CLK1_HUMAN
ID CLK1_HUMAN Reviewed; 484 AA.
AC P49759; B4DFW7; Q0P694; Q8N5V8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Dual specificity protein kinase CLK1;
DE EC=2.7.12.1;
DE AltName: Full=CDC-like kinase 1;
GN Name=CLK1; Synonyms=CLK;
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] (ISOFORM 1).
RX PubMed=1704889; DOI=10.1016/s0021-9258(19)67807-5;
RA Johnson K.W., Smith K.A.;
RT "Molecular cloning of a novel human cdc2/CDC28-like protein kinase.";
RL J. Biol. Chem. 266:3402-3407(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Blood, and Bone;
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 [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-140, AND IDENTIFICATION BY
RP 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61 AND SER-140, AND
RP IDENTIFICATION BY 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-140, AND
RP 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 [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, AND IDENTIFICATION BY
RP 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 [LARGE SCALE ANALYSIS] AT SER-140, AND IDENTIFICATION BY
RP 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 [16]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-61; GLY-118; SER-307 AND THR-440.
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 and may be a constituent
CC of a network of regulatory mechanisms that enable SR proteins to
CC control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates
CC the alternative splicing of tissue factor (F3) pre-mRNA in endothelial
CC cells and adenovirus E1A pre-mRNA. {ECO:0000269|PubMed:10480872,
CC ECO:0000269|PubMed:19168442}.
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: Regulates splicing of its own pre-mRNA according
CC to its kinase activity; increased expression of the catalytically
CC active form influences splicing to generate the catalytically inactive
CC splicing variant lacking the kinase domain. Leucettine L41 inhibits its
CC kinase activity and affects the regulation of alternative splicing
CC mediated by phosphorylation of SR proteins (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PPIG and UBL5. {ECO:0000269|PubMed:12705895}.
CC -!- INTERACTION:
CC P49759; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-473775, EBI-10172290;
CC P49759; O76083: PDE9A; NbExp=3; IntAct=EBI-473775, EBI-742764;
CC P49759-3; Q8N2M8: CLASRP; NbExp=3; IntAct=EBI-11981867, EBI-751069;
CC P49759-3; P49760: CLK2; NbExp=5; IntAct=EBI-11981867, EBI-750020;
CC P49759-3; Q92997: DVL3; NbExp=3; IntAct=EBI-11981867, EBI-739789;
CC P49759-3; P60371: KRTAP10-6; NbExp=3; IntAct=EBI-11981867, EBI-12012928;
CC P49759-3; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-11981867, EBI-10172290;
CC P49759-3; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-11981867, EBI-739832;
CC P49759-3; O76083-2: PDE9A; NbExp=3; IntAct=EBI-11981867, EBI-11524542;
CC P49759-3; O14492-2: SH2B2; NbExp=3; IntAct=EBI-11981867, EBI-19952306;
CC P49759-3; A7MD48: SRRM4; NbExp=3; IntAct=EBI-11981867, EBI-3867173;
CC P49759-3; Q07955: SRSF1; NbExp=3; IntAct=EBI-11981867, EBI-398920;
CC P49759-3; O75494: SRSF10; NbExp=3; IntAct=EBI-11981867, EBI-353655;
CC P49759-3; P84103: SRSF3; NbExp=3; IntAct=EBI-11981867, EBI-372557;
CC P49759-3; Q16629: SRSF7; NbExp=3; IntAct=EBI-11981867, EBI-398885;
CC P49759-3; P62995: TRA2B; NbExp=5; IntAct=EBI-11981867, EBI-725485;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=P49759-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P49759-2; Sequence=VSP_004852, VSP_004853;
CC Name=3;
CC IsoId=P49759-3; Sequence=VSP_043578;
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}.
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DR EMBL; L29219; AAA61480.1; -; mRNA.
DR EMBL; L29222; AAB59459.1; -; mRNA.
DR EMBL; AK289365; BAF82054.1; -; mRNA.
DR EMBL; AK294295; BAG57578.1; -; mRNA.
DR EMBL; AC005037; AAY14722.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70217.1; -; Genomic_DNA.
DR EMBL; BC028149; AAH28149.1; -; mRNA.
DR EMBL; BC031549; AAH31549.1; -; mRNA.
DR CCDS; CCDS2331.1; -. [P49759-1]
DR CCDS; CCDS54427.1; -. [P49759-3]
DR PIR; S53641; S53641.
DR RefSeq; NP_001155879.1; NM_001162407.1. [P49759-3]
DR RefSeq; NP_004062.2; NM_004071.3. [P49759-1]
DR PDB; 1Z57; X-ray; 1.70 A; A=148-484.
DR PDB; 2VAG; X-ray; 1.80 A; A=148-484.
DR PDB; 5J1V; X-ray; 2.52 A; A/B/C=148-484.
DR PDB; 5J1W; X-ray; 2.42 A; A/B/C=148-484.
DR PDB; 5X8I; X-ray; 1.90 A; A/B=148-484.
DR PDB; 6FT8; X-ray; 1.45 A; A=148-484.
DR PDB; 6FT9; X-ray; 1.87 A; A/B/C=148-484.
DR PDB; 6FYO; X-ray; 2.32 A; A=148-484.
DR PDB; 6G33; X-ray; 2.05 A; A/B/C=148-484.
DR PDB; 6I5H; X-ray; 1.49 A; A=148-484.
DR PDB; 6I5I; X-ray; 1.60 A; A=148-484.
DR PDB; 6I5K; X-ray; 2.30 A; A/B/C=148-484.
DR PDB; 6I5L; X-ray; 2.55 A; A/B/C=148-484.
DR PDB; 6KHD; X-ray; 2.70 A; A/B/C=1-484.
DR PDB; 6Q8K; X-ray; 2.29 A; A=148-484.
DR PDB; 6Q8P; X-ray; 3.00 A; A/B/C=148-484.
DR PDB; 6QTY; X-ray; 1.65 A; A=148-484.
DR PDB; 6R3D; X-ray; 1.85 A; A=148-484.
DR PDB; 6R6E; X-ray; 2.25 A; A=148-484.
DR PDB; 6R6X; X-ray; 2.05 A; A=148-484.
DR PDB; 6R8J; X-ray; 1.75 A; A=148-484.
DR PDB; 6RAA; X-ray; 2.10 A; A=148-484.
DR PDB; 6TW2; X-ray; 1.80 A; E=148-484.
DR PDB; 6YTA; X-ray; 2.30 A; A=148-484.
DR PDB; 6YTD; X-ray; 2.00 A; A=148-484.
DR PDB; 6YTE; X-ray; 2.30 A; C=148-484.
DR PDB; 6YTG; X-ray; 1.95 A; A=148-484.
DR PDB; 6YTI; X-ray; 2.40 A; A=148-484.
DR PDB; 6Z4Z; X-ray; 2.07 A; A/B/C=148-484.
DR PDB; 6Z50; X-ray; 1.60 A; A=148-484.
DR PDB; 6ZLN; X-ray; 1.70 A; A=148-484.
DR PDB; 7AK3; X-ray; 2.50 A; A=148-484.
DR PDB; 7OPG; X-ray; 1.93 A; A/B/C=148-484.
DR PDBsum; 1Z57; -.
DR PDBsum; 2VAG; -.
DR PDBsum; 5J1V; -.
DR PDBsum; 5J1W; -.
DR PDBsum; 5X8I; -.
DR PDBsum; 6FT8; -.
DR PDBsum; 6FT9; -.
DR PDBsum; 6FYO; -.
DR PDBsum; 6G33; -.
DR PDBsum; 6I5H; -.
DR PDBsum; 6I5I; -.
DR PDBsum; 6I5K; -.
DR PDBsum; 6I5L; -.
DR PDBsum; 6KHD; -.
DR PDBsum; 6Q8K; -.
DR PDBsum; 6Q8P; -.
DR PDBsum; 6QTY; -.
DR PDBsum; 6R3D; -.
DR PDBsum; 6R6E; -.
DR PDBsum; 6R6X; -.
DR PDBsum; 6R8J; -.
DR PDBsum; 6RAA; -.
DR PDBsum; 6TW2; -.
DR PDBsum; 6YTA; -.
DR PDBsum; 6YTD; -.
DR PDBsum; 6YTE; -.
DR PDBsum; 6YTG; -.
DR PDBsum; 6YTI; -.
DR PDBsum; 6Z4Z; -.
DR PDBsum; 6Z50; -.
DR PDBsum; 6ZLN; -.
DR PDBsum; 7AK3; -.
DR PDBsum; 7OPG; -.
DR AlphaFoldDB; P49759; -.
DR SMR; P49759; -.
DR BioGRID; 107606; 197.
DR IntAct; P49759; 54.
DR MINT; P49759; -.
DR STRING; 9606.ENSP00000394734; -.
DR BindingDB; P49759; -.
DR ChEMBL; CHEMBL4224; -.
DR DrugBank; DB06376; CHGN111.
DR DrugBank; DB04367; Debromohymenialdisine.
DR DrugBank; DB08691; ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P49759; -.
DR GuidetoPHARMACOLOGY; 1990; -.
DR GlyGen; P49759; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49759; -.
DR PhosphoSitePlus; P49759; -.
DR BioMuta; CLK1; -.
DR DMDM; 206729857; -.
DR EPD; P49759; -.
DR jPOST; P49759; -.
DR MassIVE; P49759; -.
DR MaxQB; P49759; -.
DR PaxDb; P49759; -.
DR PeptideAtlas; P49759; -.
DR PRIDE; P49759; -.
DR ProteomicsDB; 56090; -. [P49759-1]
DR ProteomicsDB; 56091; -. [P49759-2]
DR ProteomicsDB; 56092; -. [P49759-3]
DR Antibodypedia; 34923; 224 antibodies from 29 providers.
DR DNASU; 1195; -.
DR Ensembl; ENST00000321356.9; ENSP00000326830.4; ENSG00000013441.17. [P49759-1]
DR Ensembl; ENST00000432425.5; ENSP00000400487.1; ENSG00000013441.17. [P49759-2]
DR Ensembl; ENST00000434813.3; ENSP00000394734.2; ENSG00000013441.17. [P49759-3]
DR GeneID; 1195; -.
DR KEGG; hsa:1195; -.
DR MANE-Select; ENST00000321356.9; ENSP00000326830.4; NM_004071.4; NP_004062.2.
DR UCSC; uc002uwe.3; human. [P49759-1]
DR CTD; 1195; -.
DR DisGeNET; 1195; -.
DR GeneCards; CLK1; -.
DR HGNC; HGNC:2068; CLK1.
DR HPA; ENSG00000013441; Low tissue specificity.
DR MIM; 601951; gene.
DR neXtProt; NX_P49759; -.
DR OpenTargets; ENSG00000013441; -.
DR PharmGKB; PA26594; -.
DR VEuPathDB; HostDB:ENSG00000013441; -.
DR eggNOG; KOG0671; Eukaryota.
DR GeneTree; ENSGT00940000159722; -.
DR HOGENOM; CLU_126079_0_0_1; -.
DR InParanoid; P49759; -.
DR OMA; YHNHSSK; -.
DR OrthoDB; 915778at2759; -.
DR PhylomeDB; P49759; -.
DR TreeFam; TF101041; -.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; P49759; -.
DR SignaLink; P49759; -.
DR SIGNOR; P49759; -.
DR BioGRID-ORCS; 1195; 8 hits in 1113 CRISPR screens.
DR ChiTaRS; CLK1; human.
DR EvolutionaryTrace; P49759; -.
DR GeneWiki; CLK1; -.
DR GenomeRNAi; 1195; -.
DR Pharos; P49759; Tchem.
DR PRO; PR:P49759; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P49759; protein.
DR Bgee; ENSG00000013441; Expressed in granulocyte and 201 other tissues.
DR ExpressionAtlas; P49759; baseline and differential.
DR Genevisible; P49759; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:ProtInc.
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:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0043484; P:regulation of RNA splicing; 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..484
FT /note="Dual specificity protein kinase CLK1"
FT /id="PRO_0000085866"
FT DOMAIN 161..477
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..100
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..136
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 288
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 167..175
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 191
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 138
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MAAGRRPASALWPERRGSPLRGDLLGFQNVREPSSCGETLSGM (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043578"
FT VAR_SEQ 131..136
FT /note="KSHRRK -> MKLLIL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7990150"
FT /id="VSP_004852"
FT VAR_SEQ 137..484
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7990150"
FT /id="VSP_004853"
FT VARIANT 61
FT /note="S -> F (in dbSNP:rs55989135)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040409"
FT VARIANT 99
FT /note="N -> D (in dbSNP:rs6735666)"
FT /id="VAR_046551"
FT VARIANT 118
FT /note="R -> G (in dbSNP:rs56135616)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040410"
FT VARIANT 307
FT /note="P -> S (in dbSNP:rs35412475)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040411"
FT VARIANT 440
FT /note="M -> T (in dbSNP:rs35393352)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040412"
FT VARIANT 459
FT /note="E -> G (in dbSNP:rs12709)"
FT /id="VAR_051620"
FT CONFLICT 432
FT /note="R -> A (in Ref. 1; AAA61480)"
FT /evidence="ECO:0000305"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:6FT8"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 161..170
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:6FT8"
FT TURN 181..185
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 197..216
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:6Z50"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 236..242
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 248..254
FT /evidence="ECO:0007829|PDB:6FT8"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 262..281
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 301..306
FT /evidence="ECO:0007829|PDB:6FT8"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 311..317
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:6YTE"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 348..351
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 359..374
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 384..395
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 400..405
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:6FT8"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:6YTI"
FT HELIX 424..432
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 436..439
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 445..457
FT /evidence="ECO:0007829|PDB:6FT8"
FT TURN 462..464
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 468..471
FT /evidence="ECO:0007829|PDB:6FT8"
FT HELIX 475..481
FT /evidence="ECO:0007829|PDB:6FT8"
SQ SEQUENCE 484 AA; 57291 MW; F34B5B44988BD118 CRC64;
MRHSKRTYCP DWDDKDWDYG KWRSSSSHKR RKRSHSSAQE NKRCKYNHSK MCDSHYLESR
SINEKDYHSR RYIDEYRNDY TQGCEPGHRQ RDHESRYQNH SSKSSGRSGR SSYKSKHRIH
HSTSHRRSHG KSHRRKRTRS VEDDEEGHLI CQSGDVLSAR YEIVDTLGEG AFGKVVECID
HKAGGRHVAV KIVKNVDRYC EAARSEIQVL EHLNTTDPNS TFRCVQMLEW FEHHGHICIV
FELLGLSTYD FIKENGFLPF RLDHIRKMAY QICKSVNFLH SNKLTHTDLK PENILFVQSD
YTEAYNPKIK RDERTLINPD IKVVDFGSAT YDDEHHSTLV STRHYRAPEV ILALGWSQPC
DVWSIGCILI EYYLGFTVFP THDSKEHLAM MERILGPLPK HMIQKTRKRK YFHHDRLDWD
EHSSAGRYVS RRCKPLKEFM LSQDVEHERL FDLIQKMLEY DPAKRITLRE ALKHPFFDLL
KKSI
