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P22518 (CLK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity protein kinase CLK1

EC=2.7.12.1
Alternative name(s):
CDC-like kinase 1
Protein kinase STY
Gene names
Name:Clk1
Synonyms:Clk, Sty
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length483 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA. Ref.9 Ref.10

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Regulates splicing of its own pre-mRNA according to its kinase activity; increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins. Ref.10 Ref.12

Subunit structure

Interacts with PPIG and UBL5 By similarity.

Subcellular location

Nucleus Ref.9.

Post-translational modification

Autophosphorylates on all three types of residues.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

lubXQ5ZRQ03EBI-6479117,EBI-6402540From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P22518-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: P22518-2)

Also known as: Clk1T;

The sequence of this isoform differs from the canonical sequence as follows:
     130-135: KSHRRK → MKLLIL
     136-483: Missing.
Note: Lacks the kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 483483Dual specificity protein kinase CLK1
PRO_0000085867

Regions

Domain160 – 476317Protein kinase
Nucleotide binding166 – 1749ATP By similarity
Motif29 – 335Nuclear localization signal Potential

Sites

Active site2871Proton acceptor By similarity
Binding site1901ATP By similarity

Amino acid modifications

Modified residue611Phosphoserine By similarity
Modified residue1391Phosphoserine Ref.11

Natural variations

Alternative sequence130 – 1356KSHRRK → MKLLIL in isoform Short.
VSP_004854
Alternative sequence136 – 483348Missing in isoform Short.
VSP_004855

Experimental info

Mutagenesis1901K → R: Loss of activity. Ref.1
Sequence conflict3791P → S in AAA40151. Ref.2
Sequence conflict4481L → F in CAA40473. Ref.1
Sequence conflict4531I → V in CAA40473. Ref.1
Sequence conflict4561M → I in CAA40473. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 96FEBC20EC90D8E8

FASTA48357,093
        10         20         30         40         50         60 
MRHSKRTYCP DWDERDWDYG TWRSSSSHKR KKRSHSSARE QKRCRYDHSK TTDSYYLESR 

        70         80         90        100        110        120 
SINEKAYHSR RYVDEYRNDY MGYEPGHPYG EPGSRYQMHS SKSSGRSGRS SYKSKHRSRH 

       130        140        150        160        170        180 
HTSQHHSHGK SHRRKRSRSV EDDEEGHLIC QSGDVLSARY EIVDTLGEGA FGKVVECIDH 

       190        200        210        220        230        240 
KVGGRRVAVK IVKNVDRYCE AAQSEIQVLE HLNTTDPHST FRCVQMLEWF EHRGHICIVF 

       250        260        270        280        290        300 
ELLGLSTYDF IKENSFLPFR MDHIRKMAYQ ICKSVNFLHS NKLTHTDLKP ENILFVKSDY 

       310        320        330        340        350        360 
TEAYNPKMKR DERTIVNPDI KVVDFGSATY DDEHHSTLVS TRHYRAPEVI LALGWSQPCD 

       370        380        390        400        410        420 
VWSIGCILIE YYLGFTVFPT HDSREHLAMM ERILGPLPKH MIQKTRKRRY FHHDRLDWDE 

       430        440        450        460        470        480 
HSSAGRYVSR RCKPLKEFML SQDAEHELLF DLIGKMLEYD PAKRITLKEA LKHPFFYPLK 


KHT 

« Hide

Isoform Short (Clk1T) [UniParc].

Checksum: 44BBA47A5D09705A
Show »

FASTA13516,318

References

« Hide 'large scale' references
[1]"A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators."
Ben-David Y., Letwin K., Tannock L., Bernstein A., Pawson T.
EMBO J. 10:317-325(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), MUTAGENESIS OF LYS-190.
[2]"STY, a tyrosine-phosphorylating enzyme with sequence homology to serine/threonine kinases."
Howell B.W., Afar D.E., Lew J., Douville E.M., Icely P.L., Gray D.A., Bell J.C.
Mol. Cell. Biol. 11:568-572(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Alternative splicing of STY, a nuclear dual specificity kinase."
Duncan P.I., Howell B.W., Marius R.M., Drmanic S., Douville E.M., Bell J.C.
J. Biol. Chem. 270:21524-21531(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[4]"Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases."
Hanes J.J., der Kammer H., Klaudiny J.J., Scheit K.H.
J. Mol. Biol. 244:665-672(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[5]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Strain: C57BL/6J.
[6]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
Tissue: Brain.
[8]"The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution."
Colwill K., Pawson T., Andrews B., Prasad J., Manley J.L., Bell J.C., Duncan P.I.
EMBO J. 15:265-275(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[9]"Characterization and comparison of four serine- and arginine-rich (SR) protein kinases."
Nayler O., Stamm S., Ullrich A.
Biochem. J. 326:693-700(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[10]"In vivo regulation of alternative pre-mRNA splicing by the Clk1 protein kinase."
Duncan P.I., Stojdl D.F., Marius R.M., Bell J.C.
Mol. Cell. Biol. 17:5996-6001(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[11]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[12]"Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing."
Debdab M., Carreaux F., Renault S., Soundararajan M., Fedorov O., Filippakopoulos P., Lozach O., Babault L., Tahtouh T., Baratte B., Ogawa Y., Hagiwara M., Eisenreich A., Rauch U., Knapp S., Meijer L., Bazureau J.P.
J. Med. Chem. 54:4172-4186(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X57186 mRNA. Translation: CAA40473.1.
M38381 mRNA. Translation: AAA40151.1.
U21209 mRNA. Translation: AAC52257.1.
L29221 mRNA. Translation: AAA61485.1.
AK135765 mRNA. Translation: BAE22647.1.
CH466548 Genomic DNA. Translation: EDL00074.1.
BC145905 mRNA. Translation: AAI45906.1.
BC145911 mRNA. Translation: AAI45912.1.
CCDSCCDS35577.1. [P22518-1]
PIRA39676.
I49275.
RefSeqNP_001036099.1. NM_001042634.2. [P22518-1]
UniGeneMm.1761.

3D structure databases

ProteinModelPortalP22518.
SMRP22518. Positions 147-481.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP22518. 1 interaction.

Chemistry

BindingDBP22518.
ChEMBLCHEMBL1075280.

PTM databases

PhosphoSiteP22518.

Proteomic databases

PRIDEP22518.

Protocols and materials databases

DNASU12747.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034868; ENSMUSP00000034868; ENSMUSG00000026034. [P22518-1]
ENSMUST00000148330; ENSMUSP00000137649; ENSMUSG00000026034. [P22518-2]
ENSMUST00000151338; ENSMUSP00000137815; ENSMUSG00000026034. [P22518-2]
GeneID12747.
KEGGmmu:12747.
UCSCuc007bbs.2. mouse. [P22518-1]

Organism-specific databases

CTD1195.
MGIMGI:107403. Clk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00580000081366.
HOGENOMHOG000203417.
HOVERGENHBG107720.
InParanoidQ3UXB6.
KOK08823.
OMAMLSQDVE.
OrthoDBEOG7TBC1V.
TreeFamTF101041.

Enzyme and pathway databases

BRENDA2.7.12.1. 3474.

Gene expression databases

ArrayExpressP22518.
BgeeP22518.
CleanExMM_CLK1.
GenevestigatorP22518.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCLK1. mouse.
NextBio282070.
PROP22518.
SOURCESearch...

Entry information

Entry nameCLK1_MOUSE
AccessionPrimary (citable) accession number: P22518
Secondary accession number(s): A6H6K2, Q3UXB6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot