CLK2_HUMAN
ID CLK2_HUMAN Reviewed; 499 AA.
AC P49760; B1AVS9; B5MBX6; Q96CQ0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Dual specificity protein kinase CLK2;
DE EC=2.7.12.1;
DE AltName: Full=CDC-like kinase 2;
GN Name=CLK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=7990150; DOI=10.1006/jmbi.1994.1763;
RA Hanes J.J., der Kammer H., Klaudiny J.J., Scheit K.H.;
RT "Characterization by cDNA cloning of two new human protein kinases.
RT Evidence by sequence comparison of a new family of mammalian protein
RT kinases.";
RL J. Mol. Biol. 244:665-672(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=9331372; DOI=10.1101/gr.7.10.1020;
RA Winfield S.L., Tayebi N., Martin B.M., Ginns E.I., Sidransky E.;
RT "Identification of three additional genes contiguous to the
RT glucocerebrosidase locus on chromosome 1q21: implications for Gaucher
RT disease.";
RL Genome Res. 7:1020-1026(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Lung, and Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=8910305; DOI=10.1074/jbc.271.44.27299;
RA Lee K., Du C., Horn M., Rabinow L.;
RT "Activity and autophosphorylation of LAMMER protein kinases.";
RL J. Biol. Chem. 271:27299-27303(1996).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=9637771; DOI=10.1006/excr.1998.4083;
RA Duncan P.I., Stojdl D.F., Marius R.M., Scheit K.H., Bell J.C.;
RT "The Clk2 and Clk3 dual-specificity protein kinases regulate the
RT intranuclear distribution of SR proteins and influence pre-mRNA splicing.";
RL Exp. Cell Res. 241:300-308(1998).
RN [7]
RP FUNCTION.
RX PubMed=10480872; DOI=10.1074/jbc.274.38.26697;
RA Moeslein F.M., Myers M.P., Landreth G.E.;
RT "The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the
RT tyrosine phosphatase, PTP-1B.";
RL J. Biol. Chem. 274:26697-26704(1999).
RN [8]
RP INTERACTION WITH UBL5.
RX PubMed=12705895; DOI=10.1016/s0006-291x(03)00549-7;
RA Kantham L., Kerr-Bayles L., Godde N., Quick M., Webb R., Sunderland T.,
RA Bond J., Walder K., Augert G., Collier G.;
RT "Beacon interacts with cdc2/cdc28-like kinases.";
RL Biochem. Biophys. Res. Commun. 304:125-129(2003).
RN [9]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP FUNCTION, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=19168442; DOI=10.1161/circresaha.108.183905;
RA Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S.,
RA Poller W., Schultheiss H.P., Rauch U.;
RT "Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of
RT tissue factor in human endothelial cells.";
RL Circ. Res. 104:589-599(2009).
RN [13]
RP INTERACTION WITH RBMX.
RX PubMed=19282290; DOI=10.1074/jbc.m901026200;
RA Heinrich B., Zhang Z., Raitskin O., Hiller M., Benderska N., Hartmann A.M.,
RA Bracco L., Elliott D., Ben-Ari S., Soreq H., Sperling J., Sperling R.,
RA Stamm S.;
RT "Heterogeneous nuclear ribonucleoprotein G regulates splice site selection
RT by binding to CC(A/C)-rich regions in pre-mRNA.";
RL J. Biol. Chem. 284:14303-14315(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142 AND TYR-153, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION AT SER-34 AND THR-127, AND INTERACTION WITH AKT1.
RX PubMed=20682768; DOI=10.1074/jbc.m110.122044;
RA Nam S.Y., Seo H.H., Park H.S., An S., Kim J.Y., Yang K.H., Kim C.S.,
RA Jeong M., Jin Y.W.;
RT "Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls
RT cell survival after ionizing radiation.";
RL J. Biol. Chem. 285:31157-31163(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-142, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28289210; DOI=10.1073/pnas.1700082114;
RA Kulkarni P., Jolly M.K., Jia D., Mooney S.M., Bhargava A., Kagohara L.T.,
RA Chen Y., Hao P., He Y., Veltri R.W., Grishaev A., Weninger K., Levine H.,
RA Orban J.;
RT "Phosphorylation-induced conformational dynamics in an intrinsically
RT disordered protein and potential role in phenotypic heterogeneity.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E2644-E2653(2017).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 135-496.
RG Structural genomics consortium (SGC);
RT "Structure of human cdc2-like kinase 2 (clk2).";
RL Submitted (AUG-2010) to the PDB data bank.
CC -!- FUNCTION: Dual specificity kinase acting on both serine/threonine and
CC tyrosine-containing substrates. Phosphorylates serine- and arginine-
CC rich (SR) proteins of the spliceosomal complex. May be a constituent of
CC a network of regulatory mechanisms that enable SR proteins to control
CC RNA splicing and can cause redistribution of SR proteins from speckles
CC to a diffuse nucleoplasmic distribution. Acts as a suppressor of
CC hepatic gluconeogenesis and glucose output by repressing PPARGC1A
CC transcriptional activity on gluconeogenic genes via its
CC phosphorylation. Phosphorylates PPP2R5B thereby stimulating the
CC assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to
CC dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3.
CC Regulates the alternative splicing of tissue factor (F3) pre-mRNA in
CC endothelial cells. Phosphorylates PAGE4 at several serine and threonine
CC residues and this phosphorylation attenuates the ability of PAGE4 to
CC potentiate the transcriptional activator activity of JUN
CC (PubMed:28289210). {ECO:0000269|PubMed:10480872,
CC ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:28289210,
CC ECO:0000269|PubMed:8910305, ECO:0000269|PubMed:9637771}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- ACTIVITY REGULATION: 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole
CC (DRB) inhibits autophosphorylation. TG003 inhibits its kinase activity
CC and affects the regulation of alternative splicing mediated by
CC phosphorylation of SR proteins (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with RBMX. Interacts with AKT1 and UBL5.
CC {ECO:0000269|PubMed:12705895, ECO:0000269|PubMed:19282290,
CC ECO:0000269|PubMed:20682768}.
CC -!- INTERACTION:
CC P49760; Q9BZE9: ASPSCR1; NbExp=3; IntAct=EBI-750020, EBI-1993677;
CC P49760; Q8WUQ7: CACTIN; NbExp=3; IntAct=EBI-750020, EBI-348479;
CC P49760; Q8N2M8: CLASRP; NbExp=3; IntAct=EBI-750020, EBI-751069;
CC P49760; P49759-3: CLK1; NbExp=5; IntAct=EBI-750020, EBI-11981867;
CC P49760; P49760: CLK2; NbExp=6; IntAct=EBI-750020, EBI-750020;
CC P49760; P49761: CLK3; NbExp=13; IntAct=EBI-750020, EBI-745579;
CC P49760; Q8N684: CPSF7; NbExp=3; IntAct=EBI-750020, EBI-746909;
CC P49760; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-750020, EBI-742054;
CC P49760; P42892: ECE1; NbExp=6; IntAct=EBI-750020, EBI-2859983;
CC P49760; Q08426: EHHADH; NbExp=3; IntAct=EBI-750020, EBI-2339219;
CC P49760; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-750020, EBI-10172181;
CC P49760; Q9BX10: GTPBP2; NbExp=3; IntAct=EBI-750020, EBI-6115579;
CC P49760; O95198: KLHL2; NbExp=6; IntAct=EBI-750020, EBI-746999;
CC P49760; Q8TBB1: LNX1; NbExp=8; IntAct=EBI-750020, EBI-739832;
CC P49760; Q9P127: LUZP4; NbExp=6; IntAct=EBI-750020, EBI-10198848;
CC P49760; Q9BYD3: MRPL4; NbExp=3; IntAct=EBI-750020, EBI-721368;
CC P49760; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-750020, EBI-398874;
CC P49760; P04553: PRM1; NbExp=3; IntAct=EBI-750020, EBI-13066730;
CC P49760; Q8NAV1: PRPF38A; NbExp=3; IntAct=EBI-750020, EBI-715374;
CC P49760; Q14498: RBM39; NbExp=9; IntAct=EBI-750020, EBI-395290;
CC P49760; O76064: RNF8; NbExp=5; IntAct=EBI-750020, EBI-373337;
CC P49760; D3DU92: RNPS1; NbExp=5; IntAct=EBI-750020, EBI-10176640;
CC P49760; Q15287: RNPS1; NbExp=5; IntAct=EBI-750020, EBI-395959;
CC P49760; Q9BUV0: RSRP1; NbExp=13; IntAct=EBI-750020, EBI-745604;
CC P49760; O00560: SDCBP; NbExp=3; IntAct=EBI-750020, EBI-727004;
CC P49760; Q8TAD8: SNIP1; NbExp=8; IntAct=EBI-750020, EBI-749336;
CC P49760; P08621: SNRNP70; NbExp=5; IntAct=EBI-750020, EBI-1049228;
CC P49760; P78362: SRPK2; NbExp=3; IntAct=EBI-750020, EBI-593303;
CC P49760; Q8IYB3: SRRM1; NbExp=6; IntAct=EBI-750020, EBI-1055880;
CC P49760; P84103: SRSF3; NbExp=3; IntAct=EBI-750020, EBI-372557;
CC P49760; B2RWP4: TACC2; NbExp=3; IntAct=EBI-750020, EBI-14211313;
CC P49760; P14373: TRIM27; NbExp=4; IntAct=EBI-750020, EBI-719493;
CC P49760; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-750020, EBI-9867283;
CC P49760; Q01081-2: U2AF1; NbExp=3; IntAct=EBI-750020, EBI-10176676;
CC P49760; Q7KZS0: UBE2I; NbExp=6; IntAct=EBI-750020, EBI-10180829;
CC P49760; Q96MU7: YTHDC1; NbExp=6; IntAct=EBI-750020, EBI-2849854;
CC P49760; P52737: ZNF136; NbExp=3; IntAct=EBI-750020, EBI-749129;
CC P49760; O14978: ZNF263; NbExp=3; IntAct=EBI-750020, EBI-744493;
CC P49760; Q96PQ6: ZNF317; NbExp=3; IntAct=EBI-750020, EBI-1210473;
CC P49760; Q53GI3: ZNF394; NbExp=3; IntAct=EBI-750020, EBI-10211248;
CC P49760; Q8TD17: ZNF398; NbExp=6; IntAct=EBI-750020, EBI-8643207;
CC P49760; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-750020, EBI-8489702;
CC P49760; Q8IYI8: ZNF440; NbExp=3; IntAct=EBI-750020, EBI-726439;
CC P49760; Q8WTR7: ZNF473; NbExp=3; IntAct=EBI-750020, EBI-751409;
CC P49760; Q8N8L2: ZNF491; NbExp=3; IntAct=EBI-750020, EBI-12019860;
CC P49760; Q96NG5: ZNF558; NbExp=3; IntAct=EBI-750020, EBI-373363;
CC P49760; Q96H86: ZNF764; NbExp=3; IntAct=EBI-750020, EBI-745775;
CC P49760; Q9H5H4: ZNF768; NbExp=3; IntAct=EBI-750020, EBI-1210580;
CC P49760; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-750020, EBI-11962574;
CC P49760; Q15696: ZRSR2; NbExp=8; IntAct=EBI-750020, EBI-6657923;
CC P49760; Q9Y5A6: ZSCAN21; NbExp=5; IntAct=EBI-750020, EBI-10281938;
CC P49760-3; A0A0S2Z4Z6: SRRM1; NbExp=3; IntAct=EBI-11535445, EBI-16438171;
CC P49760-3; Q8IYB3: SRRM1; NbExp=3; IntAct=EBI-11535445, EBI-1055880;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28289210}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:9637771}. Nucleus speckle
CC {ECO:0000269|PubMed:9637771}. Note=Inhibition of phosphorylation at
CC Ser-142 results in accumulation in the nuclear speckle.
CC {ECO:0000250|UniProtKB:O35491}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus speckle
CC {ECO:0000269|PubMed:9637771}. Note=Co-localizes with serine- and
CC arginine-rich (SR) proteins in the nuclear speckles.
CC {ECO:0000269|PubMed:9637771}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=P49760-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P49760-2; Sequence=VSP_004856, VSP_004857;
CC Name=3;
CC IsoId=P49760-3; Sequence=VSP_038744;
CC -!- TISSUE SPECIFICITY: Endothelial cells (PubMed:19168442). Expressed in
CC androgen-dependent prostate cancer cells (PubMed:28289210).
CC {ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:28289210}.
CC -!- PTM: Autophosphorylates on all three types of residues. Phosphorylation
CC on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or
CC insulin. Phosphorylation plays a critical role in cell proliferation
CC following low dose radiation and prevents cell death following high
CC dose radiation. Phosphorylation at Thr-344 by PKB/AKT2 induces its
CC kinase activity which is required for its stability. The
CC phosphorylation status at Ser-142 influences its subnuclear
CC localization; inhibition of phosphorylation at Ser-142 results in
CC accumulation in the nuclear speckle. {ECO:0000269|PubMed:20682768,
CC ECO:0000269|PubMed:9637771}.
CC -!- MISCELLANEOUS: [Isoform 2]: Lacks the kinase domain. May be produced at
CC very low levels due to a premature stop codon in the mRNA, leading to
CC nonsense-mediated mRNA decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. Lammer subfamily. {ECO:0000305}.
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DR EMBL; L29218; AAA61482.1; -; mRNA.
DR EMBL; L29216; AAA61481.1; -; mRNA.
DR EMBL; AF023268; AAC51817.1; -; Genomic_DNA.
DR EMBL; AL713999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014067; AAH14067.1; -; mRNA.
DR EMBL; BC053603; AAH53603.1; -; mRNA.
DR CCDS; CCDS1107.1; -. [P49760-3]
DR CCDS; CCDS72939.1; -. [P49760-1]
DR PIR; S53637; S53637.
DR PIR; S53638; S53638.
DR RefSeq; NP_001281267.1; NM_001294338.1. [P49760-1]
DR RefSeq; NP_001281268.1; NM_001294339.1.
DR RefSeq; NP_003984.2; NM_003993.3. [P49760-3]
DR PDB; 3NR9; X-ray; 2.89 A; A/B/C=135-496.
DR PDB; 5UNP; X-ray; 2.92 A; A/B=129-496.
DR PDB; 6FYI; X-ray; 2.60 A; A=132-496.
DR PDB; 6FYK; X-ray; 2.39 A; A/B/C=136-496.
DR PDB; 6FYL; X-ray; 1.95 A; A=136-496.
DR PDB; 6KHE; X-ray; 2.80 A; A=1-499.
DR PDBsum; 3NR9; -.
DR PDBsum; 5UNP; -.
DR PDBsum; 6FYI; -.
DR PDBsum; 6FYK; -.
DR PDBsum; 6FYL; -.
DR PDBsum; 6KHE; -.
DR AlphaFoldDB; P49760; -.
DR SMR; P49760; -.
DR BioGRID; 107607; 172.
DR DIP; DIP-42277N; -.
DR IntAct; P49760; 139.
DR MINT; P49760; -.
DR STRING; 9606.ENSP00000357345; -.
DR BindingDB; P49760; -.
DR ChEMBL; CHEMBL4225; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P49760; -.
DR GuidetoPHARMACOLOGY; 1991; -.
DR iPTMnet; P49760; -.
DR PhosphoSitePlus; P49760; -.
DR BioMuta; CLK2; -.
DR DMDM; 1705919; -.
DR EPD; P49760; -.
DR jPOST; P49760; -.
DR MassIVE; P49760; -.
DR MaxQB; P49760; -.
DR PaxDb; P49760; -.
DR PeptideAtlas; P49760; -.
DR PRIDE; P49760; -.
DR ProteomicsDB; 56093; -. [P49760-1]
DR ProteomicsDB; 56094; -. [P49760-2]
DR ProteomicsDB; 56095; -. [P49760-3]
DR Antibodypedia; 34187; 329 antibodies from 31 providers.
DR DNASU; 1196; -.
DR Ensembl; ENST00000361168.9; ENSP00000354856.5; ENSG00000176444.19. [P49760-3]
DR Ensembl; ENST00000368361.9; ENSP00000357345.4; ENSG00000176444.19. [P49760-1]
DR Ensembl; ENST00000572269.5; ENSP00000459461.1; ENSG00000261893.5. [P49760-3]
DR Ensembl; ENST00000574445.5; ENSP00000460443.1; ENSG00000261893.5. [P49760-1]
DR GeneID; 1196; -.
DR KEGG; hsa:1196; -.
DR MANE-Select; ENST00000368361.9; ENSP00000357345.4; NM_001294338.2; NP_001281267.1.
DR UCSC; uc001fjw.4; human. [P49760-1]
DR CTD; 1196; -.
DR DisGeNET; 1196; -.
DR GeneCards; CLK2; -.
DR HGNC; HGNC:2069; CLK2.
DR HPA; ENSG00000176444; Low tissue specificity.
DR MIM; 602989; gene.
DR neXtProt; NX_P49760; -.
DR OpenTargets; ENSG00000176444; -.
DR PharmGKB; PA26595; -.
DR VEuPathDB; HostDB:ENSG00000176444; -.
DR eggNOG; KOG0671; Eukaryota.
DR GeneTree; ENSGT00940000154947; -.
DR InParanoid; P49760; -.
DR OMA; CIVFEYY; -.
DR PhylomeDB; P49760; -.
DR TreeFam; TF101041; -.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; P49760; -.
DR SignaLink; P49760; -.
DR SIGNOR; P49760; -.
DR BioGRID-ORCS; 1196; 107 hits in 1109 CRISPR screens.
DR ChiTaRS; CLK2; human.
DR EvolutionaryTrace; P49760; -.
DR GeneWiki; CLK2; -.
DR GenomeRNAi; 1196; -.
DR Pharos; P49760; Tchem.
DR PRO; PR:P49760; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P49760; protein.
DR Bgee; ENSG00000176444; Expressed in right uterine tube and 94 other tissues.
DR ExpressionAtlas; P49760; baseline and differential.
DR Genevisible; P49760; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; IDA:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..499
FT /note="Dual specificity protein kinase CLK2"
FT /id="PRO_0000085868"
FT DOMAIN 163..479
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..34
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..67
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..129
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 290
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 169..177
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 34
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:20682768"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 99
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O35491"
FT MOD_RES 127
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:20682768"
FT MOD_RES 142
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 153
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 344
FT /note="Phosphothreonine; by PKB/AKT2"
FT /evidence="ECO:0000250|UniProtKB:O35491"
FT VAR_SEQ 134..139
FT /note="QHSSRR -> MKSLAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7990150"
FT /id="VSP_004856"
FT VAR_SEQ 134
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038744"
FT VAR_SEQ 140..499
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7990150"
FT /id="VSP_004857"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:6FYK"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:6FYK"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 163..171
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 173..182
FT /evidence="ECO:0007829|PDB:6FYL"
FT TURN 183..187
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 199..218
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:6FYK"
FT STRAND 229..235
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 238..244
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 250..256
FT /evidence="ECO:0007829|PDB:6FYL"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 264..283
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:6FYL"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 313..319
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:6KHE"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:3NR9"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 350..353
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 361..376
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 386..397
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 402..407
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:6FYL"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:6KHE"
FT HELIX 426..434
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 438..441
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 447..459
FT /evidence="ECO:0007829|PDB:6FYL"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 470..473
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 477..479
FT /evidence="ECO:0007829|PDB:6FYL"
FT HELIX 480..483
FT /evidence="ECO:0007829|PDB:3NR9"
SQ SEQUENCE 499 AA; 60090 MW; E43BBF3BAD6EF991 CRC64;
MPHPRRYHSS ERGSRGSYRE HYRSRKHKRR RSRSWSSSSD RTRRRRREDS YHVRSRSSYD
DRSSDRRVYD RRYCGSYRRN DYSRDRGDAY YDTDYRHSYE YQRENSSYRS QRSSRRKHRR
RRRRSRTFSR SSSQHSSRRA KSVEDDAEGH LIYHVGDWLQ ERYEIVSTLG EGTFGRVVQC
VDHRRGGARV ALKIIKNVEK YKEAARLEIN VLEKINEKDP DNKNLCVQMF DWFDYHGHMC
ISFELLGLST FDFLKDNNYL PYPIHQVRHM AFQLCQAVKF LHDNKLTHTD LKPENILFVN
SDYELTYNLE KKRDERSVKS TAVRVVDFGS ATFDHEHHST IVSTRHYRAP EVILELGWSQ
PCDVWSIGCI IFEYYVGFTL FQTHDNREHL AMMERILGPI PSRMIRKTRK QKYFYRGRLD
WDENTSAGRY VRENCKPLRR YLTSEAEEHH QLFDLIESML EYEPAKRLTL GEALQHPFFA
RLRAEPPNKL WDSSRDISR
