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Protein

Dual specificity protein kinase CLK2

Gene

Clk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei192 – 1921ATPPROSITE-ProRule annotation
Active sitei289 – 2891Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi168 – 1769ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
  • protein serine/threonine kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: MGI

GO - Biological processi

  • negative regulation of gluconeogenesis Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: MGI
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of RNA splicing Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • response to organic substance Source: MGI
  • response to retinoic acid Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity protein kinase CLK2 (EC:2.7.12.1)
Alternative name(s):
CDC-like kinase 2
Gene namesi
Name:Clk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1098669. Clk2.

Subcellular locationi

  • Nucleus
  • Nucleus speckle

  • Note: Inhibition of phosphorylation at Ser-141 results in accumulation in the nuclear speckle.

GO - Cellular componenti

  • nuclear speck Source: UniProtKB-SubCell
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi141 – 1411S → A or E: Loss of phosphorylation. 1 Publication

Chemistry

ChEMBLiCHEMBL1075281.
GuidetoPHARMACOLOGYi1991.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 499499Dual specificity protein kinase CLK2PRO_0000085869Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei34 – 341Phosphoserine; by PKB/AKT1By similarity
Modified residuei98 – 981Phosphoserine; by autocatalysis1 Publication
Modified residuei99 – 991Phosphotyrosine; by autocatalysis1 Publication
Modified residuei127 – 1271Phosphothreonine; by PKB/AKT1By similarity
Modified residuei141 – 1411Phosphoserine; by autocatalysisCombined sources1 Publication
Modified residuei152 – 1521PhosphotyrosineBy similarity
Modified residuei343 – 3431Phosphothreonine; by PKB/AKT21 Publication

Post-translational modificationi

Autophosphorylates on all three types of residues. Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin. Phosphorylation plays a critical role in cell proliferation following low dose radiation and prevents cell death following high dose radiation. Phosphorylation at Thr-343 by PKB/AKT2 induces its kinase activity which is required for its stability. The phosphorylation status at Ser-141 influences its subnuclear localization; inhibition of phosphorylation at Ser-141 results in accumulation in the nuclear speckle.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO35491.
MaxQBiO35491.
PaxDbiO35491.
PRIDEiO35491.

PTM databases

iPTMnetiO35491.
PhosphoSiteiO35491.

Expressioni

Inductioni

By insulin (at protein level).1 Publication

Gene expression databases

BgeeiO35491.
ExpressionAtlasiO35491. baseline and differential.
GenevisibleiO35491. MM.

Interactioni

Subunit structurei

Interacts with RBMX and UBL5 (By similarity). Interacts with AKT1.By similarity1 Publication

Protein-protein interaction databases

BioGridi198752. 1 interaction.
STRINGi10090.ENSMUSP00000113390.

Chemistry

BindingDBiO35491.

Structurei

3D structure databases

ProteinModelPortaliO35491.
SMRiO35491. Positions 135-481.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini163 – 479317Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiO35491.
KOiK08823.
OrthoDBiEOG7TBC1V.
TreeFamiTF101041.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35491-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPHPRRYHSS ERGSRGSYHE HYQSRKHKRR RSRSWSSSSD RTRRRRREDS
60 70 80 90 100
YHVRSRSSYD DHSSDRRLYD RRYCGSYRRN DYSRDRGEAY YDTDFRQSYE
110 120 130 140 150
YHRENSSYRS QRSSRRKHRR RRRRSRTFSR SSSHSSRRAK SVEDDAEGHL
160 170 180 190 200
IYHVGDWLQE RYEIVSTLGE GTFGRVVQCV DHRRGGTQVA LKIIKNVEKY
210 220 230 240 250
KEAARLEINV LEKINEKDPD NKNLCVQMFD WFDYHGHMCI SFELLGLSTF
260 270 280 290 300
DFLKDNNYLP YPIHQVRHMA FQLCQAVKFL HDNKLTHTDL KPENILFVNS
310 320 330 340 350
DYELTYNLEK KRDERSVKST AVRVVDFGSA TFDHEHHSTI VSTRHYRAPE
360 370 380 390 400
VILELGWSQP CDVWSIGCII FEYYVGFTLF QTHDNREHLA MMERILGPVP
410 420 430 440 450
SRMIRKTRKQ KYFYRGRLDW DENTSAGRYV RENCKPLRRY LTSEAEDHHQ
460 470 480 490
LFDLIENMLE YEPAKRLTLG EALQHPFFAC LRTEPPNTKL WDSSRDISR
Length:499
Mass (Da):59,987
Last modified:July 27, 2011 - v2
Checksum:i29A7196AFC7797CA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti173 – 1731F → S in AAB87508 (PubMed:9307018).Curated
Sequence conflicti188 – 1881Q → R in AAB87508 (PubMed:9307018).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033564 mRNA. Translation: AAB87508.1.
AC161600 Genomic DNA. No translation available.
CCDSiCCDS17491.1.
RefSeqiNP_031738.2. NM_007712.4.
UniGeneiMm.288098.

Genome annotation databases

EnsembliENSMUST00000121212; ENSMUSP00000113390; ENSMUSG00000068917.
GeneIDi12748.
KEGGimmu:12748.
UCSCiuc008pxt.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033564 mRNA. Translation: AAB87508.1.
AC161600 Genomic DNA. No translation available.
CCDSiCCDS17491.1.
RefSeqiNP_031738.2. NM_007712.4.
UniGeneiMm.288098.

3D structure databases

ProteinModelPortaliO35491.
SMRiO35491. Positions 135-481.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198752. 1 interaction.
STRINGi10090.ENSMUSP00000113390.

Chemistry

BindingDBiO35491.
ChEMBLiCHEMBL1075281.
GuidetoPHARMACOLOGYi1991.

PTM databases

iPTMnetiO35491.
PhosphoSiteiO35491.

Proteomic databases

EPDiO35491.
MaxQBiO35491.
PaxDbiO35491.
PRIDEiO35491.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000121212; ENSMUSP00000113390; ENSMUSG00000068917.
GeneIDi12748.
KEGGimmu:12748.
UCSCiuc008pxt.2. mouse.

Organism-specific databases

CTDi1196.
MGIiMGI:1098669. Clk2.

Phylogenomic databases

eggNOGiKOG0671. Eukaryota.
ENOG410XQF2. LUCA.
GeneTreeiENSGT00580000081366.
HOGENOMiHOG000203417.
HOVERGENiHBG107720.
InParanoidiO35491.
KOiK08823.
OrthoDBiEOG7TBC1V.
TreeFamiTF101041.

Enzyme and pathway databases

BRENDAi2.7.12.1. 3474.

Miscellaneous databases

ChiTaRSiClk2. mouse.
NextBioi282076.
PROiO35491.
SOURCEiSearch...

Gene expression databases

BgeeiO35491.
ExpressionAtlasiO35491. baseline and differential.
GenevisibleiO35491. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The cellular localization of the murine serine/arginine-rich protein kinase CLK2 is regulated by serine 141 autophosphorylation."
    Nayler O., Schnorrer F., Stamm S., Ullrich A.
    J. Biol. Chem. 273:34341-34348(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-141, SUBCELLULAR LOCATION, ENZYME REGULATION, MUTAGENESIS OF SER-141.
  4. Cited for: ENZYME REGULATION.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Lung and Spleen.
  6. "Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis."
    Rodgers J.T., Haas W., Gygi S.P., Puigserver P.
    Cell Metab. 11:23-34(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT SER-98; TYR-99 AND THR-343, INDUCTION, INTERACTION WITH AKT1.
  7. "Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt."
    Rodgers J.T., Vogel R.O., Puigserver P.
    Mol. Cell 41:471-479(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiCLK2_MOUSE
AccessioniPrimary (citable) accession number: O35491
Secondary accession number(s): E9Q721
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.