CLK1_MOUSE
ID CLK1_MOUSE Reviewed; 483 AA.
AC P22518; A6H6K2; Q3UXB6;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Dual specificity protein kinase CLK1;
DE EC=2.7.12.1;
DE AltName: Full=CDC-like kinase 1;
DE AltName: Full=Protein kinase STY;
GN Name=Clk1; Synonyms=Clk, Sty;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND MUTAGENESIS OF LYS-190.
RX PubMed=1825055; DOI=10.1002/j.1460-2075.1991.tb07952.x;
RA Ben-David Y., Letwin K., Tannock L., Bernstein A., Pawson T.;
RT "A mammalian protein kinase with potential for serine/threonine and
RT tyrosine phosphorylation is related to cell cycle regulators.";
RL EMBO J. 10:317-325(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1986248; DOI=10.1128/mcb.11.1.568-572.1991;
RA Howell B.W., Afar D.E., Lew J., Douville E.M., Icely P.L., Gray D.A.,
RA Bell J.C.;
RT "STY, a tyrosine-phosphorylating enzyme with sequence homology to
RT serine/threonine kinases.";
RL Mol. Cell. Biol. 11:568-572(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RX PubMed=7665564; DOI=10.1074/jbc.270.37.21524;
RA Duncan P.I., Howell B.W., Marius R.M., Drmanic S., Douville E.M.,
RA Bell J.C.;
RT "Alternative splicing of STY, a nuclear dual specificity kinase.";
RL J. Biol. Chem. 270:21524-21531(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Brain;
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 [8]
RP CHARACTERIZATION.
RX PubMed=8617202; DOI=10.1002/j.1460-2075.1996.tb00357.x;
RA Colwill K., Pawson T., Andrews B., Prasad J., Manley J.L., Bell J.C.,
RA Duncan P.I.;
RT "The Clk/Sty protein kinase phosphorylates SR splicing factors and
RT regulates their intranuclear distribution.";
RL EMBO J. 15:265-275(1996).
RN [9]
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=9307018; DOI=10.1042/bj3260693;
RA Nayler O., Stamm S., Ullrich A.;
RT "Characterization and comparison of four serine- and arginine-rich (SR)
RT protein kinases.";
RL Biochem. J. 326:693-700(1997).
RN [10]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=9315658; DOI=10.1128/mcb.17.10.5996;
RA Duncan P.I., Stojdl D.F., Marius R.M., Bell J.C.;
RT "In vivo regulation of alternative pre-mRNA splicing by the Clk1 protein
RT kinase.";
RL Mol. Cell. Biol. 17:5996-6001(1997).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP ACTIVITY REGULATION.
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).
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:9307018,
CC ECO:0000269|PubMed:9315658}.
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.
CC {ECO:0000269|PubMed:21615147, ECO:0000269|PubMed:9315658}.
CC -!- SUBUNIT: Interacts with PPIG and UBL5. {ECO:0000250}.
CC -!- INTERACTION:
CC P22518; Q5ZRQ0: lubX; Xeno; NbExp=3; IntAct=EBI-6479117, EBI-6402540;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9307018}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P22518-1; Sequence=Displayed;
CC Name=Short; Synonyms=Clk1T;
CC IsoId=P22518-2; Sequence=VSP_004854, VSP_004855;
CC -!- PTM: Autophosphorylates on all three types of residues.
CC {ECO:0000269|PubMed:9307018}.
CC -!- MISCELLANEOUS: [Isoform Short]: Lacks the kinase domain. {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; X57186; CAA40473.1; -; mRNA.
DR EMBL; M38381; AAA40151.1; -; mRNA.
DR EMBL; U21209; AAC52257.1; -; mRNA.
DR EMBL; L29221; AAA61485.1; -; mRNA.
DR EMBL; AK135765; BAE22647.1; -; mRNA.
DR EMBL; CH466548; EDL00074.1; -; Genomic_DNA.
DR EMBL; BC145905; AAI45906.1; -; mRNA.
DR EMBL; BC145911; AAI45912.1; -; mRNA.
DR CCDS; CCDS35577.1; -. [P22518-1]
DR PIR; A39676; A39676.
DR PIR; I49275; I49275.
DR RefSeq; NP_001036099.1; NM_001042634.2. [P22518-1]
DR AlphaFoldDB; P22518; -.
DR SMR; P22518; -.
DR BioGRID; 198751; 9.
DR IntAct; P22518; 2.
DR MINT; P22518; -.
DR STRING; 10090.ENSMUSP00000034868; -.
DR BindingDB; P22518; -.
DR ChEMBL; CHEMBL1075280; -.
DR GuidetoPHARMACOLOGY; 1990; -.
DR iPTMnet; P22518; -.
DR PhosphoSitePlus; P22518; -.
DR EPD; P22518; -.
DR jPOST; P22518; -.
DR MaxQB; P22518; -.
DR PaxDb; P22518; -.
DR PeptideAtlas; P22518; -.
DR PRIDE; P22518; -.
DR ProteomicsDB; 283524; -. [P22518-1]
DR ProteomicsDB; 283525; -. [P22518-2]
DR Antibodypedia; 34923; 224 antibodies from 29 providers.
DR DNASU; 12747; -.
DR Ensembl; ENSMUST00000034868; ENSMUSP00000034868; ENSMUSG00000026034. [P22518-1]
DR Ensembl; ENSMUST00000148330; ENSMUSP00000137649; ENSMUSG00000026034. [P22518-2]
DR Ensembl; ENSMUST00000151338; ENSMUSP00000137815; ENSMUSG00000026034. [P22518-2]
DR GeneID; 12747; -.
DR KEGG; mmu:12747; -.
DR UCSC; uc007bbs.2; mouse. [P22518-1]
DR CTD; 1195; -.
DR MGI; MGI:107403; Clk1.
DR VEuPathDB; HostDB:ENSMUSG00000026034; -.
DR eggNOG; KOG0671; Eukaryota.
DR GeneTree; ENSGT00940000159722; -.
DR HOGENOM; CLU_000288_5_16_1; -.
DR InParanoid; P22518; -.
DR OMA; YHNHSSK; -.
DR OrthoDB; 915778at2759; -.
DR PhylomeDB; P22518; -.
DR TreeFam; TF101041; -.
DR BRENDA; 2.7.12.1; 3474.
DR BioGRID-ORCS; 12747; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Clk1; mouse.
DR PRO; PR:P22518; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P22518; protein.
DR Bgee; ENSMUSG00000026034; Expressed in secondary palatal shelf and 260 other tissues.
DR Genevisible; P22518; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043484; P:regulation of RNA splicing; ISO:MGI.
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 Alternative splicing; ATP-binding; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tyrosine-protein kinase.
FT CHAIN 1..483
FT /note="Dual specificity protein kinase CLK1"
FT /id="PRO_0000085867"
FT DOMAIN 160..476
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 29..33
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..25
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 109..135
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 287
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 166..174
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 190
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:0000250|UniProtKB:P49759"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 130..135
FT /note="KSHRRK -> MKLLIL (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7665564, ECO:0000303|PubMed:7990150"
FT /id="VSP_004854"
FT VAR_SEQ 136..483
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7665564, ECO:0000303|PubMed:7990150"
FT /id="VSP_004855"
FT MUTAGEN 190
FT /note="K->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1825055"
FT CONFLICT 379
FT /note="P -> S (in Ref. 2; AAA40151)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="L -> F (in Ref. 1; CAA40473)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="I -> V (in Ref. 1; CAA40473)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="M -> I (in Ref. 1; CAA40473)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 483 AA; 57093 MW; 96FEBC20EC90D8E8 CRC64;
MRHSKRTYCP DWDERDWDYG TWRSSSSHKR KKRSHSSARE QKRCRYDHSK TTDSYYLESR
SINEKAYHSR RYVDEYRNDY MGYEPGHPYG EPGSRYQMHS SKSSGRSGRS SYKSKHRSRH
HTSQHHSHGK SHRRKRSRSV EDDEEGHLIC QSGDVLSARY EIVDTLGEGA FGKVVECIDH
KVGGRRVAVK IVKNVDRYCE AAQSEIQVLE HLNTTDPHST FRCVQMLEWF EHRGHICIVF
ELLGLSTYDF IKENSFLPFR MDHIRKMAYQ ICKSVNFLHS NKLTHTDLKP ENILFVKSDY
TEAYNPKMKR DERTIVNPDI KVVDFGSATY DDEHHSTLVS TRHYRAPEVI LALGWSQPCD
VWSIGCILIE YYLGFTVFPT HDSREHLAMM ERILGPLPKH MIQKTRKRRY FHHDRLDWDE
HSSAGRYVSR RCKPLKEFML SQDAEHELLF DLIGKMLEYD PAKRITLKEA LKHPFFYPLK
KHT
