CLK3_HUMAN
ID CLK3_HUMAN Reviewed; 638 AA.
AC P49761; D3DW59; Q53Y48; Q9BRS3; Q9BUJ7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Dual specificity protein kinase CLK3;
DE EC=2.7.12.1;
DE AltName: Full=CDC-like kinase 3;
GN Name=CLK3;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 137-638 (ISOFORM 4).
RC TISSUE=Cervix, and Placenta;
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 [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 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-155; SER-157; SER-224 AND
RP SER-226, AND IDENTIFICATION BY 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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-224 AND SER-226, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157; SER-197; SER-199 AND
RP SER-283, AND 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 284-638.
RA Papagrigoriou E., Rellos P., Das S., Ugochukwu E., Turnbull A.,
RA von Delft F., Bunkoczi G., Sobott F., Bullock A., Fedorov O., Gileadi C.,
RA Savitsky P., Edwards A., Aerrowsmith C., Weigel J., Sundstrom M., Knapp S.;
RT "Crystal structure of CLK3.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 275-627.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the phosphorylated clk3.";
RL Submitted (APR-2007) to the PDB data bank.
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 275-632 IN COMPLEX WITH
RP LEUCETTINE L41.
RX PubMed=21615147; DOI=10.1021/jm200274d;
RA Debdab M., Carreaux F., Renault S., Soundararajan M., Fedorov O.,
RA Filippakopoulos P., Lozach O., Babault L., Tahtouh T., Baratte B.,
RA Ogawa Y., Hagiwara M., Eisenreich A., Rauch U., Knapp S., Meijer L.,
RA Bazureau J.P.;
RT "Leucettines, a class of potent inhibitors of cdc2-like kinases and dual
RT specificity, tyrosine phosphorylation regulated kinases derived from the
RT marine sponge leucettamine B: modulation of alternative pre-RNA splicing.";
RL J. Med. Chem. 54:4172-4186(2011).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-486; ARG-607 AND TRP-628.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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. Phosphorylates SRSF1 and
CC SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-
CC mRNA in endothelial cells. {ECO:0000269|PubMed:19168442,
CC 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: Leucettine L41 inhibits its kinase activity and
CC affects the regulation of alternative splicing mediated by
CC phosphorylation of SR proteins.
CC -!- INTERACTION:
CC P49761; Q8IWX8: CHERP; NbExp=3; IntAct=EBI-745579, EBI-2555370;
CC P49761; Q8N2M8: CLASRP; NbExp=4; IntAct=EBI-745579, EBI-751069;
CC P49761; P49760: CLK2; NbExp=13; IntAct=EBI-745579, EBI-750020;
CC P49761; P49761: CLK3; NbExp=6; IntAct=EBI-745579, EBI-745579;
CC P49761; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-745579, EBI-742054;
CC P49761; P17509: HOXB6; NbExp=6; IntAct=EBI-745579, EBI-741308;
CC P49761; P09629: HOXB7; NbExp=6; IntAct=EBI-745579, EBI-1248457;
CC P49761; P09017: HOXC4; NbExp=3; IntAct=EBI-745579, EBI-3923226;
CC P49761; P08238: HSP90AB1; NbExp=2; IntAct=EBI-745579, EBI-352572;
CC P49761; Q0VD86: INCA1; NbExp=3; IntAct=EBI-745579, EBI-6509505;
CC P49761; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-745579, EBI-739832;
CC P49761; Q5M9Q1: NKAPL; NbExp=3; IntAct=EBI-745579, EBI-11423380;
CC P49761; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-745579, EBI-398874;
CC P49761; P29728: OAS2; NbExp=4; IntAct=EBI-745579, EBI-10211452;
CC P49761; P29728-2: OAS2; NbExp=5; IntAct=EBI-745579, EBI-12270678;
CC P49761; P38159: RBMX; NbExp=3; IntAct=EBI-745579, EBI-743526;
CC P49761; P0DJD3: RBMY1A1; NbExp=3; IntAct=EBI-745579, EBI-8638511;
CC P49761; Q15415: RBMY1J; NbExp=3; IntAct=EBI-745579, EBI-8642021;
CC P49761; O76064: RNF8; NbExp=3; IntAct=EBI-745579, EBI-373337;
CC P49761; Q15287: RNPS1; NbExp=4; IntAct=EBI-745579, EBI-395959;
CC P49761; Q9BUV0: RSRP1; NbExp=11; IntAct=EBI-745579, EBI-745604;
CC P49761; P10523: SAG; NbExp=3; IntAct=EBI-745579, EBI-1642180;
CC P49761; O00560: SDCBP; NbExp=6; IntAct=EBI-745579, EBI-727004;
CC P49761; O14492-2: SH2B2; NbExp=3; IntAct=EBI-745579, EBI-19952306;
CC P49761; Q8TAD8: SNIP1; NbExp=3; IntAct=EBI-745579, EBI-749336;
CC P49761; Q16560-2: SNRNP35; NbExp=3; IntAct=EBI-745579, EBI-12938570;
CC P49761; P78362: SRPK2; NbExp=5; IntAct=EBI-745579, EBI-593303;
CC P49761; O75494: SRSF10; NbExp=3; IntAct=EBI-745579, EBI-353655;
CC P49761; P84103: SRSF3; NbExp=3; IntAct=EBI-745579, EBI-372557;
CC P49761; Q9BRL6-2: SRSF8; NbExp=3; IntAct=EBI-745579, EBI-10976394;
CC P49761; O43463: SUV39H1; NbExp=2; IntAct=EBI-745579, EBI-349968;
CC P49761; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-745579, EBI-717399;
CC P49761; P62995: TRA2B; NbExp=8; IntAct=EBI-745579, EBI-725485;
CC P49761; O14978: ZNF263; NbExp=3; IntAct=EBI-745579, EBI-744493;
CC P49761; Q8WTR7: ZNF473; NbExp=3; IntAct=EBI-745579, EBI-751409;
CC P49761; Q9ULD5: ZNF777; NbExp=3; IntAct=EBI-745579, EBI-11975599;
CC P49761; Q9Y2P0: ZNF835; NbExp=5; IntAct=EBI-745579, EBI-5667516;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus. Cytoplasm {ECO:0000250}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus speckle. Note=Co-localizes
CC with serine- and arginine-rich (SR) proteins in the nuclear speckles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=4;
CC IsoId=P49761-4; Sequence=Displayed;
CC Name=1; Synonyms=Long;
CC IsoId=P49761-1; Sequence=VSP_026138;
CC Name=2; Synonyms=Short;
CC IsoId=P49761-2; Sequence=VSP_026138, VSP_004858, VSP_004859;
CC Name=3;
CC IsoId=P49761-3; Sequence=VSP_026138, VSP_004860;
CC -!- TISSUE SPECIFICITY: Endothelial cells. {ECO:0000269|PubMed:19168442}.
CC -!- PTM: Autophosphorylates on all three types of residues. {ECO:0000250}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAH02555.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH19881.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L29220; AAA61483.1; -; mRNA.
DR EMBL; L29217; AAA61484.1; -; mRNA.
DR EMBL; BT006993; AAP35639.1; -; mRNA.
DR EMBL; AC100835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99321.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99322.1; -; Genomic_DNA.
DR EMBL; BC002555; AAH02555.1; ALT_INIT; mRNA.
DR EMBL; BC006103; AAH06103.1; -; mRNA.
DR EMBL; BC019881; AAH19881.1; ALT_INIT; mRNA.
DR CCDS; CCDS10265.1; -. [P49761-1]
DR CCDS; CCDS45304.1; -. [P49761-1]
DR PIR; S53639; S53639.
DR PIR; S53640; S53640.
DR RefSeq; NP_001123500.1; NM_001130028.1. [P49761-1]
DR RefSeq; NP_003983.2; NM_003992.4. [P49761-1]
DR RefSeq; XP_016877398.1; XM_017021909.1.
DR RefSeq; XP_016877399.1; XM_017021910.1.
DR PDB; 2EU9; X-ray; 1.53 A; A=284-638.
DR PDB; 2EXE; X-ray; 2.35 A; A=275-631.
DR PDB; 2WU6; X-ray; 1.92 A; A=275-632.
DR PDB; 2WU7; X-ray; 2.25 A; A=275-632.
DR PDB; 3RAW; X-ray; 2.09 A; A/B=275-632.
DR PDB; 6FT7; X-ray; 2.02 A; A/B=275-632.
DR PDB; 6FYP; X-ray; 2.29 A; A=275-632.
DR PDB; 6FYR; X-ray; 1.42 A; A=275-632.
DR PDB; 6KHF; X-ray; 2.60 A; A=149-638.
DR PDB; 6RCT; X-ray; 2.32 A; A/B=275-632.
DR PDB; 6YTW; X-ray; 2.00 A; A/B=275-632.
DR PDB; 6YTY; X-ray; 1.76 A; A=275-632.
DR PDB; 6YU1; X-ray; 1.90 A; a/c=275-632.
DR PDB; 6Z2V; X-ray; 2.60 A; A=275-632.
DR PDB; 6Z51; X-ray; 1.92 A; A=275-632.
DR PDB; 6Z52; X-ray; 2.12 A; A/B=275-632.
DR PDB; 6Z53; X-ray; 1.65 A; A=275-632.
DR PDB; 6Z54; X-ray; 1.73 A; A=275-632.
DR PDB; 6Z55; X-ray; 1.70 A; A/B=275-632.
DR PDBsum; 2EU9; -.
DR PDBsum; 2EXE; -.
DR PDBsum; 2WU6; -.
DR PDBsum; 2WU7; -.
DR PDBsum; 3RAW; -.
DR PDBsum; 6FT7; -.
DR PDBsum; 6FYP; -.
DR PDBsum; 6FYR; -.
DR PDBsum; 6KHF; -.
DR PDBsum; 6RCT; -.
DR PDBsum; 6YTW; -.
DR PDBsum; 6YTY; -.
DR PDBsum; 6YU1; -.
DR PDBsum; 6Z2V; -.
DR PDBsum; 6Z51; -.
DR PDBsum; 6Z52; -.
DR PDBsum; 6Z53; -.
DR PDBsum; 6Z54; -.
DR PDBsum; 6Z55; -.
DR AlphaFoldDB; P49761; -.
DR SMR; P49761; -.
DR BioGRID; 107609; 191.
DR IntAct; P49761; 139.
DR MINT; P49761; -.
DR STRING; 9606.ENSP00000378505; -.
DR BindingDB; P49761; -.
DR ChEMBL; CHEMBL4226; -.
DR DrugBank; DB08691; ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB07664; K-00546.
DR DrugCentral; P49761; -.
DR GuidetoPHARMACOLOGY; 1992; -.
DR iPTMnet; P49761; -.
DR PhosphoSitePlus; P49761; -.
DR BioMuta; CLK3; -.
DR DMDM; 148887358; -.
DR EPD; P49761; -.
DR jPOST; P49761; -.
DR MassIVE; P49761; -.
DR MaxQB; P49761; -.
DR PaxDb; P49761; -.
DR PeptideAtlas; P49761; -.
DR PRIDE; P49761; -.
DR ProteomicsDB; 56096; -. [P49761-4]
DR ProteomicsDB; 56097; -. [P49761-1]
DR ProteomicsDB; 56098; -. [P49761-2]
DR ProteomicsDB; 56099; -. [P49761-3]
DR Antibodypedia; 26974; 160 antibodies from 27 providers.
DR DNASU; 1198; -.
DR Ensembl; ENST00000345005.8; ENSP00000344112.4; ENSG00000179335.20. [P49761-1]
DR Ensembl; ENST00000395066.9; ENSP00000378505.4; ENSG00000179335.20. [P49761-1]
DR Ensembl; ENST00000483723.5; ENSP00000431825.1; ENSG00000179335.20. [P49761-2]
DR GeneID; 1198; -.
DR KEGG; hsa:1198; -.
DR MANE-Select; ENST00000395066.9; ENSP00000378505.4; NM_001130028.2; NP_001123500.2. [P49761-1]
DR UCSC; uc002ayg.4; human. [P49761-4]
DR CTD; 1198; -.
DR DisGeNET; 1198; -.
DR GeneCards; CLK3; -.
DR HGNC; HGNC:2071; CLK3.
DR HPA; ENSG00000179335; Low tissue specificity.
DR MIM; 602990; gene.
DR neXtProt; NX_P49761; -.
DR OpenTargets; ENSG00000179335; -.
DR PharmGKB; PA26597; -.
DR VEuPathDB; HostDB:ENSG00000179335; -.
DR eggNOG; KOG0671; Eukaryota.
DR GeneTree; ENSGT00940000160359; -.
DR HOGENOM; CLU_000288_5_16_1; -.
DR InParanoid; P49761; -.
DR PhylomeDB; P49761; -.
DR TreeFam; TF101041; -.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; P49761; -.
DR SignaLink; P49761; -.
DR SIGNOR; P49761; -.
DR BioGRID-ORCS; 1198; 28 hits in 1110 CRISPR screens.
DR ChiTaRS; CLK3; human.
DR EvolutionaryTrace; P49761; -.
DR GeneWiki; CLK3_(gene); -.
DR GenomeRNAi; 1198; -.
DR Pharos; P49761; Tchem.
DR PRO; PR:P49761; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P49761; protein.
DR Bgee; ENSG00000179335; Expressed in lower esophagus mucosa and 191 other tissues.
DR ExpressionAtlas; P49761; baseline and differential.
DR Genevisible; P49761; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
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; ISS: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:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; IDA: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; Cytoplasm;
KW Cytoplasmic vesicle; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..638
FT /note="Dual specificity protein kinase CLK3"
FT /id="PRO_0000085870"
FT DOMAIN 304..620
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..226
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..266
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 431
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 310..318
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 334
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 155
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..148
FT /note="Missing (in isoform 1, isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7990150, ECO:0000303|Ref.2"
FT /id="VSP_026138"
FT VAR_SEQ 272..300
FT /note="RSQQSSKRSSRSVEDDKEGHLVCRIGDWL -> MRLWGTWVKAPLARWWSAW
FT TMPEGSLRLP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7990150"
FT /id="VSP_004858"
FT VAR_SEQ 301..638
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7990150"
FT /id="VSP_004859"
FT VAR_SEQ 306..328
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004860"
FT VARIANT 486
FT /note="R -> C (in dbSNP:rs975796055)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040413"
FT VARIANT 607
FT /note="Q -> R (in dbSNP:rs910378995)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045579"
FT VARIANT 628
FT /note="R -> W (in dbSNP:rs920443187)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_045580"
FT CONFLICT 280..281
FT /note="SS -> TG (in Ref. 1; AAA61484)"
FT /evidence="ECO:0000305"
FT HELIX 277..282
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:6RCT"
FT TURN 301..303
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 304..313
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 316..323
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 340..359
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:6KHF"
FT STRAND 370..376
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 379..385
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 391..397
FT /evidence="ECO:0007829|PDB:6FYR"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 405..424
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 437..440
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 444..448
FT /evidence="ECO:0007829|PDB:6FYR"
FT TURN 450..453
FT /evidence="ECO:0007829|PDB:6Z55"
FT STRAND 456..460
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:2EXE"
FT STRAND 473..477
FT /evidence="ECO:0007829|PDB:6KHF"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 491..494
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 502..517
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 527..538
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 543..548
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 552..554
FT /evidence="ECO:0007829|PDB:6FYR"
FT STRAND 564..566
FT /evidence="ECO:0007829|PDB:6RCT"
FT HELIX 567..575
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 579..582
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 588..600
FT /evidence="ECO:0007829|PDB:6FYR"
FT TURN 605..607
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 611..614
FT /evidence="ECO:0007829|PDB:6FYR"
FT HELIX 618..622
FT /evidence="ECO:0007829|PDB:6FYR"
FT TURN 625..628
FT /evidence="ECO:0007829|PDB:6FYR"
SQ SEQUENCE 638 AA; 73515 MW; D3B60A9DB4ECEC94 CRC64;
MPVLSARRRE LADHAGSGRR SGPSPTARSG PHLSALRAQP ARAAHLSGRG TYVRRDTAGG
GPGQARPLGP PGTSLLGRGA RRSGEGWCPG AFESGARAAR PPSRVEPRLA TAASREGAGL
PRAEVAAGSG RGARSGEWGL AAAGAWETMH HCKRYRSPEP DPYLSYRWKR RRSYSREHEG
RLRYPSRREP PPRRSRSRSH DRLPYQRRYR ERRDSDTYRC EERSPSFGED YYGPSRSRHR
RRSRERGPYR TRKHAHHCHK RRTRSCSSAS SRSQQSSKRS SRSVEDDKEG HLVCRIGDWL
QERYEIVGNL GEGTFGKVVE CLDHARGKSQ VALKIIRNVG KYREAARLEI NVLKKIKEKD
KENKFLCVLM SDWFNFHGHM CIAFELLGKN TFEFLKENNF QPYPLPHVRH MAYQLCHALR
FLHENQLTHT DLKPENILFV NSEFETLYNE HKSCEEKSVK NTSIRVADFG SATFDHEHHT
TIVATRHYRP PEVILELGWA QPCDVWSIGC ILFEYYRGFT LFQTHENREH LVMMEKILGP
IPSHMIHRTR KQKYFYKGGL VWDENSSDGR YVKENCKPLK SYMLQDSLEH VQLFDLMRRM
LEFDPAQRIT LAEALLHPFF AGLTPEERSF HTSRNPSR
