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Protein

Dual specificity protein kinase CLK2

Gene

Clk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei192ATPPROSITE-ProRule annotation1
Active sitei289Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi168 – 176ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1098669 Clk2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi141S → A or E: Loss of phosphorylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1075281
GuidetoPHARMACOLOGYi1991

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858691 – 499Dual specificity protein kinase CLK2Add BLAST499

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Phosphoserine; by PKB/AKT1By similarity1
Modified residuei98Phosphoserine; by autocatalysis1 Publication1
Modified residuei99Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei127Phosphothreonine; by PKB/AKT1By similarity1
Modified residuei141Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei152PhosphotyrosineBy similarity1
Modified residuei343Phosphothreonine; by PKB/AKT21 Publication1

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
PhosphoSitePlusiO35491

Expressioni

Inductioni

By insulin (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000068917 Expressed in 275 organ(s), highest expression level in embryo
ExpressionAtlasiO35491 baseline and differential
GenevisibleiO35491 MM

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198752, 1 interactor
STRINGi10090.ENSMUSP00000113390

Chemistry databases

BindingDBiO35491

Structurei

3D structure databases

ProteinModelPortaliO35491
SMRiO35491
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini163 – 479Protein kinasePROSITE-ProRule annotationAdd BLAST317

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0671 Eukaryota
ENOG410XQF2 LUCA
GeneTreeiENSGT00580000081366
HOGENOMiHOG000203417
HOVERGENiHBG107720
InParanoidiO35491
KOiK08823
TreeFamiTF101041

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WHX0F8WHX0_MOUSE
Dual-specificity protein kinase CLK...
Clk2
498Annotation score:
E9Q5Y1E9Q5Y1_MOUSE
Dual-specificity protein kinase CLK...
Clk2
500Annotation score:
D3Z4P7D3Z4P7_MOUSE
Dual-specificity protein kinase CLK...
Clk2
249Annotation score:
D3Z7L4D3Z7L4_MOUSE
Dual-specificity protein kinase CLK...
Clk2
56Annotation score:
D6RG48D6RG48_MOUSE
Dual-specificity protein kinase CLK...
Clk2
136Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti173F → S in AAB87508 (PubMed:9307018).Curated1
Sequence conflicti188Q → R in AAB87508 (PubMed:9307018).Curated1

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198752, 1 interactor
STRINGi10090.ENSMUSP00000113390

Chemistry databases

BindingDBiO35491
ChEMBLiCHEMBL1075281
GuidetoPHARMACOLOGYi1991

PTM databases

iPTMnetiO35491
PhosphoSitePlusiO35491

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
TreeFamiTF101041

Enzyme and pathway databases

BRENDAi2.7.12.1 3474

Miscellaneous databases

ChiTaRSiClk2 mouse
PROiPR:O35491
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000068917 Expressed in 275 organ(s), highest expression level in embryo
ExpressionAtlasiO35491 baseline and differential
GenevisibleiO35491 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLK2_MOUSE
AccessioniPrimary (citable) accession number: O35491
Secondary accession number(s): E9Q721
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 137 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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