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 02-SEP-2026, entry version 229. 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=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, 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=4; 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=15; 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=14; IntAct=EBI-750020, EBI-745604; CC P49760; O00560: SDCBP; NbExp=3; IntAct=EBI-750020, EBI-727004; CC P49760; Q8TAD8: SNIP1; NbExp=9; IntAct=EBI-750020, EBI-749336; CC P49760; P08621: SNRNP70; NbExp=7; 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=4; 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=7; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001294338.2. [P49760-1] DR RefSeq; NP_001281268.1; NM_001294339.2. DR RefSeq; NP_003984.2; NM_003993.4. [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 AlphaFoldDB; P49760; -. DR MDposit; P49760; -. DR MDRepo; P49760; -. DR SMR; P49760; -. DR BioGRID; 107607; 210. DR DIP; DIP-42277N; -. DR FunCoup; P49760; 3224. DR IntAct; P49760; 181. DR MINT; P49760; -. DR NDEx; IQUERY-CP-CLK2; 3 NDEx IQuery Curated Pathways. 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 CPTAC; CPTAC-3158; -. DR jPOST; P49760; -. DR MassIVE; P49760; -. DR PaxDb; 9606-ENSP00000357345; -. DR PeptideAtlas; P49760; -. DR ProteomicsDB; 56093; -. [P49760-1] DR ProteomicsDB; 56094; -. [P49760-2] DR ProteomicsDB; 56095; -. [P49760-3] DR Pumba; P49760; -. DR Antibodypedia; 34187; 327 antibodies from 33 providers. DR DNASU; 1196; -. DR Ensembl; ENST00000361168.9; ENSP00000354856.5; ENSG00000176444.20. [P49760-3] DR Ensembl; ENST00000368361.9; ENSP00000357345.4; ENSG00000176444.20. [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 AGR; HGNC:2069; -. DR ClinPGx; PA26595; -. DR CTD; 1196; -. DR DisGeNET; 1196; -. DR GeneCards; CLK2; -. DR HGNC; HGNC:2069; CLK2. DR HPA; ENSG00000176444; Low tissue specificity. DR MalaCards; CLK2; -. DR MIM; 602989; gene. DR OpenTargets; ENSG00000176444; -. DR VEuPathDB; HostDB:ENSG00000176444; -. DR eggNOG; KOG0671; Eukaryota. DR GeneTree; ENSGT00940000154947; -. DR InParanoid; P49760; -. DR OMA; RHHIQSF; -. DR OrthoDB; 1924787at2759; -. DR PAN-GO; P49760; 4 GO annotations based on evolutionary models. DR PhylomeDB; P49760; -. DR BRENDA; 2.7.12.1; 2681. DR PathwayCommons; P49760; -. DR SignaLink; P49760; -. DR SIGNOR; P49760; -. DR Agora; ENSG00000176444; -. DR BioGRID-ORCS; 1196; 111 hits in 1197 CRISPR screens. DR CD-CODE; 804901D1; Nuclear speckle. 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 96 other cell types or tissues. DR ExpressionAtlas; P49760; baseline and differential. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; EXP:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. 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: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 CDD; cd14215; PKc_CLK2; 1. DR FunFam; 1.10.510.10:FF:000145; Dual specificity protein kinase CLK2; 1. DR FunFam; 3.30.200.20:FF:000061; Dual specificity protein kinase CLK2; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR051175; CLK_kinases. 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 PANTHER; PTHR45646:SF6; DUAL SPECIFICITY PROTEIN KINASE CLK2; 1. DR PANTHER; PTHR45646; SERINE/THREONINE-PROTEIN KINASE DOA-RELATED; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PDBsum; 3NR9; -. DR PDBsum; 5UNP; -. DR PDBsum; 6FYI; -. DR PDBsum; 6FYK; -. DR PDBsum; 6FYL; -. DR PDBsum; 6KHE; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW 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 8..21 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 22..33 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 47..67 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 112..127 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 HELIX 150..152 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 188..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 260..263 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 337..339 FT /evidence="ECO:0007829|PDB:6FYL" 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 399..401 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 //