CLK3_MOUSE
ID CLK3_MOUSE Reviewed; 638 AA.
AC O35492; Q3TJU0; Q3UIF5; Q3V463; Q5U4I1; Q8C1V1;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 166.
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 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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Brain, Kidney, Placenta, Thymus, and Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 139-638.
RC TISSUE=Olfactory epithelium;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 141-638, FUNCTION, PHOSPHORYLATION, AND
RP 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 [4]
RP TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=10585269; DOI=10.1006/excr.1999.4655;
RA Menegay H., Moeslein F., Landreth G.;
RT "The dual specificity protein kinase CLK3 is abundantly expressed in mature
RT mouse spermatozoa.";
RL Exp. Cell Res. 253:463-473(1999).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157; SER-224 AND SER-226, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen, and
RC 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 [6]
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. 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:9307018}.
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 Evidence={ECO:0000269|PubMed:10585269};
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; Evidence={ECO:0000269|PubMed:10585269};
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. {ECO:0000269|PubMed:21615147}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasmic vesicle,
CC secretory vesicle, acrosome.
CC -!- TISSUE SPECIFICITY: Present at high levels in testis and ovary. In
CC testis, expression is restricted to elongated, maturing spermatozoa.
CC Also present in spleen, brain, lung and liver (at protein level).
CC {ECO:0000269|PubMed:10585269}.
CC -!- PTM: Autophosphorylates on all three types of residues.
CC {ECO:0000269|PubMed:9307018}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. Lammer subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB87509.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH85084.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC41138.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE21937.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE32308.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE39405.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE39405.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK090215; BAC41138.1; ALT_INIT; mRNA.
DR EMBL; AK133936; BAE21937.1; ALT_INIT; mRNA.
DR EMBL; AK146942; BAE27551.1; -; mRNA.
DR EMBL; AK154003; BAE32308.1; ALT_INIT; mRNA.
DR EMBL; AK167300; BAE39405.1; ALT_SEQ; mRNA.
DR EMBL; AK009908; BAE43216.1; -; mRNA.
DR EMBL; BC085084; AAH85084.1; ALT_INIT; mRNA.
DR EMBL; AF033565; AAB87509.1; ALT_INIT; mRNA.
DR RefSeq; NP_031739.3; NM_007713.4.
DR RefSeq; XP_006510802.1; XM_006510739.3.
DR RefSeq; XP_017168549.1; XM_017313060.1.
DR AlphaFoldDB; O35492; -.
DR SMR; O35492; -.
DR BioGRID; 221868; 7.
DR IntAct; O35492; 1.
DR MINT; O35492; -.
DR STRING; 10090.ENSMUSP00000067341; -.
DR BindingDB; O35492; -.
DR ChEMBL; CHEMBL1075282; -.
DR GuidetoPHARMACOLOGY; 1992; -.
DR iPTMnet; O35492; -.
DR PhosphoSitePlus; O35492; -.
DR EPD; O35492; -.
DR jPOST; O35492; -.
DR MaxQB; O35492; -.
DR PaxDb; O35492; -.
DR PeptideAtlas; O35492; -.
DR PRIDE; O35492; -.
DR ProteomicsDB; 283304; -.
DR Antibodypedia; 26974; 160 antibodies from 27 providers.
DR DNASU; 102414; -.
DR Ensembl; ENSMUST00000065330; ENSMUSP00000067341; ENSMUSG00000032316.
DR GeneID; 102414; -.
DR KEGG; mmu:102414; -.
DR UCSC; uc009pvr.1; mouse.
DR CTD; 1198; -.
DR MGI; MGI:1098670; Clk3.
DR VEuPathDB; HostDB:ENSMUSG00000032316; -.
DR eggNOG; KOG0671; Eukaryota.
DR GeneTree; ENSGT00940000160359; -.
DR HOGENOM; CLU_000288_5_16_1; -.
DR InParanoid; O35492; -.
DR OMA; HTHHCHK; -.
DR OrthoDB; 915778at2759; -.
DR PhylomeDB; O35492; -.
DR TreeFam; TF101041; -.
DR BRENDA; 2.7.12.1; 3474.
DR BioGRID-ORCS; 102414; 6 hits in 78 CRISPR screens.
DR ChiTaRS; Clk3; mouse.
DR PRO; PR:O35492; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O35492; protein.
DR Bgee; ENSMUSG00000032316; Expressed in thymus and 268 other tissues.
DR ExpressionAtlas; O35492; baseline and differential.
DR Genevisible; O35492; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
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; 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; IDA:UniProtKB.
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 ATP-binding; Cytoplasm; Cytoplasmic vesicle; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..638
FT /note="Dual specificity protein kinase CLK3"
FT /id="PRO_0000085871"
FT DOMAIN 304..620
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..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:0000250|UniProtKB:P49761"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49761"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49761"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49761"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49761"
FT CONFLICT 68
FT /note="P -> T (in Ref. 1; BAE39405)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="S -> T (in Ref. 3; AAB87509)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="T -> L (in Ref. 1; BAE43216)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="T -> A (in Ref. 1; BAC41138)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 638 AA; 73798 MW; 3CE7BFD35FB09A3C CRC64;
MPVLSARRKR LASTAGPRRG SGPSLAVRWV PPLGPEPSSD RGRAPMRPRG PTCSTTRRGA
GRGPRLLPGP PGRDLHRCRP DPGGAGQSPR VCEFGARAVR PLGRVEPGPP TAASREGAVL
PRAEARAGSG RGARSGEWGL AAAGAWETMH HCKRYRSPEP DPYLSYRWKR RRSYSREHEG
RLRYPSRREP PPRRSRSRSH DRIPYQRRYR EHRDSDTYRC EERSPSFGED CYGSSRSRHR
RRSRERAPYR 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 HSSRNPSR
