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Protein

Dual specificity protein kinase CLK2

Gene

CLK2

Organism
Homo sapiens (Human)
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.4 Publications

Caution

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei193ATPPROSITE-ProRule annotation1
Active sitei290Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi169 – 177ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

  • negative regulation of gluconeogenesis Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of RNA splicing Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • response to retinoic acid Source: Ensembl

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
SignaLinkiP49760
SIGNORiP49760

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000176444.18
HGNCiHGNC:2069 CLK2
MIMi602989 gene
neXtProtiNX_P49760

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

Organism-specific databases

DisGeNETi1196
OpenTargetsiENSG00000176444
PharmGKBiPA26595

Chemistry databases

ChEMBLiCHEMBL4225
GuidetoPHARMACOLOGYi1991

Polymorphism and mutation databases

BioMutaiCLK2
DMDMi1705919

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858681 – 499Dual specificity protein kinase CLK2Add BLAST499

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Phosphoserine; by PKB/AKT11 Publication1
Modified residuei98PhosphoserineCombined sources1
Modified residuei99Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei127Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei142Phosphoserine; by autocatalysisCombined sources1
Modified residuei153PhosphotyrosineCombined sources1
Modified residuei344Phosphothreonine; by PKB/AKT2By similarity1

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-344 by PKB/AKT2 induces its kinase activity which is required for its stability. The phosphorylation status at Ser-142 influences its subnuclear localization; inhibition of phosphorylation at Ser-142 results in accumulation in the nuclear speckle.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP49760
PaxDbiP49760
PeptideAtlasiP49760
PRIDEiP49760

PTM databases

iPTMnetiP49760
PhosphoSitePlusiP49760

Expressioni

Tissue specificityi

Endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000176444
CleanExiHS_CLK2
ExpressionAtlasiP49760 baseline and differential
GenevisibleiP49760 HS

Organism-specific databases

HPAiHPA055366
HPA059507

Interactioni

Subunit structurei

Interacts with RBMX. Interacts with AKT1 and UBL5.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi107607110 interactors.
DIPiDIP-42277N
IntActiP49760 83 interactors.
MINTiP49760
STRINGi9606.ENSP00000354856

Chemistry databases

BindingDBiP49760

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni146 – 149Combined sources4
Turni160 – 162Combined sources3
Beta strandi163 – 172Combined sources10
Beta strandi175 – 182Combined sources8
Turni183 – 187Combined sources5
Beta strandi189 – 195Combined sources7
Helixi199 – 218Combined sources20
Beta strandi229 – 235Combined sources7
Beta strandi238 – 244Combined sources7
Helixi250 – 256Combined sources7
Turni257 – 259Combined sources3
Helixi264 – 283Combined sources20
Helixi293 – 295Combined sources3
Beta strandi296 – 299Combined sources4
Turni309 – 311Combined sources3
Beta strandi317 – 319Combined sources3
Beta strandi323 – 325Combined sources3
Beta strandi332 – 336Combined sources5
Helixi345 – 347Combined sources3
Helixi350 – 353Combined sources4
Helixi361 – 376Combined sources16
Helixi386 – 397Combined sources12
Helixi402 – 407Combined sources6
Helixi411 – 413Combined sources3
Helixi426 – 434Combined sources9
Helixi438 – 441Combined sources4
Helixi447 – 459Combined sources13
Turni464 – 466Combined sources3
Helixi470 – 475Combined sources6
Helixi477 – 479Combined sources3
Helixi480 – 483Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NR9X-ray2.89A/B/C135-496[»]
ProteinModelPortaliP49760
SMRiP49760
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49760

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
InParanoidiP49760
KOiK08823
OMAiLGMCVYD
OrthoDBiEOG09370FW4
PhylomeDBiP49760
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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49760-1) [UniParc]FASTAAdd to basket
Also known as: Long

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.

« Hide

        10         20         30         40         50
MPHPRRYHSS ERGSRGSYRE HYRSRKHKRR RSRSWSSSSD RTRRRRREDS
60 70 80 90 100
YHVRSRSSYD DRSSDRRVYD RRYCGSYRRN DYSRDRGDAY YDTDYRHSYE
110 120 130 140 150
YQRENSSYRS QRSSRRKHRR RRRRSRTFSR SSSQHSSRRA KSVEDDAEGH
160 170 180 190 200
LIYHVGDWLQ ERYEIVSTLG EGTFGRVVQC VDHRRGGARV ALKIIKNVEK
210 220 230 240 250
YKEAARLEIN VLEKINEKDP DNKNLCVQMF DWFDYHGHMC ISFELLGLST
260 270 280 290 300
FDFLKDNNYL PYPIHQVRHM AFQLCQAVKF LHDNKLTHTD LKPENILFVN
310 320 330 340 350
SDYELTYNLE KKRDERSVKS TAVRVVDFGS ATFDHEHHST IVSTRHYRAP
360 370 380 390 400
EVILELGWSQ PCDVWSIGCI IFEYYVGFTL FQTHDNREHL AMMERILGPI
410 420 430 440 450
PSRMIRKTRK QKYFYRGRLD WDENTSAGRY VRENCKPLRR YLTSEAEEHH
460 470 480 490
QLFDLIESML EYEPAKRLTL GEALQHPFFA RLRAEPPNKL WDSSRDISR
Length:499
Mass (Da):60,090
Last modified:October 1, 1996 - v1
Checksum:iE43BBF3BAD6EF991
GO
Isoform 2 (identifier: P49760-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     134-139: QHSSRR → MKSLAP
     140-499: Missing.

Note: Lacks the kinase domain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:139
Mass (Da):17,569
Checksum:iCC9C9C63B3B07667
GO
Isoform 3 (identifier: P49760-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-134: Missing.

Show »
Length:498
Mass (Da):59,962
Checksum:i0A21FC66FD22DBC6
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004856134 – 139QHSSRR → MKSLAP in isoform 2. 1 Publication6
Alternative sequenceiVSP_038744134Missing in isoform 3. 1 Publication1
Alternative sequenceiVSP_004857140 – 499Missing in isoform 2. 1 PublicationAdd BLAST360

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29218 mRNA Translation: AAA61482.1
L29216 mRNA Translation: AAA61481.1
AF023268 Genomic DNA Translation: AAC51817.1
AL713999 Genomic DNA Translation: CAI95098.1
BC014067 mRNA Translation: AAH14067.1
BC053603 mRNA Translation: AAH53603.1
CCDSiCCDS1107.1 [P49760-3]
CCDS72939.1 [P49760-1]
PIRiS53637
S53638
RefSeqiNP_001281267.1, NM_001294338.1 [P49760-1]
NP_001281268.1, NM_001294339.1
NP_003984.2, NM_003993.3 [P49760-3]
UniGeneiHs.73986

Genome annotation databases

EnsembliENST00000361168; ENSP00000354856; ENSG00000176444 [P49760-3]
ENST00000368361; ENSP00000357345; ENSG00000176444 [P49760-1]
ENST00000572269; ENSP00000459461; ENSG00000261893 [P49760-3]
ENST00000574445; ENSP00000460443; ENSG00000261893 [P49760-1]
GeneIDi1196
KEGGihsa:1196
UCSCiuc001fjw.4 human [P49760-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCLK2_HUMAN
AccessioniPrimary (citable) accession number: P49760
Secondary accession number(s): B1AVS9, B5MBX6, Q96CQ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: March 28, 2018
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome