Details of the Target

General Information of Target

Target ID LDTP04298
Target Name Dual specificity protein kinase CLK2 (CLK2)
Gene Name CLK2
Gene ID 1196
Synonyms
Dual specificity protein kinase CLK2; EC 2.7.12.1; CDC-like kinase 2
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPHPRRYHSSERGSRGSYREHYRSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYD
DRSSDRRVYDRRYCGSYRRNDYSRDRGDAYYDTDYRHSYEYQRENSSYRSQRSSRRKHRR
RRRRSRTFSRSSSQHSSRRAKSVEDDAEGHLIYHVGDWLQERYEIVSTLGEGTFGRVVQC
VDHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPDNKNLCVQMFDWFDYHGHMC
ISFELLGLSTFDFLKDNNYLPYPIHQVRHMAFQLCQAVKFLHDNKLTHTDLKPENILFVN
SDYELTYNLEKKRDERSVKSTAVRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQ
PCDVWSIGCIIFEYYVGFTLFQTHDNREHLAMMERILGPIPSRMIRKTRKQKYFYRGRLD
WDENTSAGRYVRENCKPLRRYLTSEAEEHHQLFDLIESMLEYEPAKRLTLGEALQHPFFA
RLRAEPPNKLWDSSRDISR
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Protein kinase superfamily, CMGC Ser/Thr protein kinase family, Lammer subfamily
Subcellular location
Nucleus; Nucleus speckle
Function
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. Phosphorylates PAGE4 at several serine and threonine residues and this phosphorylation attenuates the ability of PAGE4 to potentiate the transcriptional activator activity of JUN.
TTD ID
T73725
Uniprot ID
P49760
DrugMap ID
TT85TPS
Ensemble ID
ENST00000361168.9
HGNC ID
HGNC:2069
ChEMBL ID
CHEMBL4225

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
EFO27 SNV: p.R138W .
HCT15 SNV: p.N80S .
KYM1 SNV: p.D49H .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C180(27.90)  LDD0209  [1]
IPM
 Probe Info  		C180(1.16)  LDD1702  [2]
IA-alkyne
 Probe Info  		C74(0.00); C180(0.00)  LDD0162  [3]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C180(1.16)  LDD1702  [2]
 LDCM0022  KB02 22RV1 C180(1.66)  LDD2243  [5]
 LDCM0023  KB03 Jurkat C180(27.90)  LDD0209  [1]
 LDCM0024  KB05 COLO792 C180(1.80)  LDD3310  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 10 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Peroxisomal bifunctional enzyme (EHHADH) Enoyl-CoA hydratase/isomerase family; 3-hydroxyacyl-CoA dehydrogenase family Q08426
Endothelin-converting enzyme 1 (ECE1) Peptidase M13 family P42892
SRSF protein kinase 2 (SRPK2) CMGC Ser/Thr protein kinase family P78362
Dual specificity protein kinase CLK2 (CLK2) CMGC Ser/Thr protein kinase family P49760
Dual specificity protein kinase CLK3 (CLK3) CMGC Ser/Thr protein kinase family P49761
E3 ubiquitin-protein ligase RNF8 (RNF8) RNF8 family O76064
GTP-binding protein 2 (GTPBP2) Classic translation factor GTPase family Q9BX10
E3 ubiquitin-protein ligase TRIM50 (TRIM50) TRIM/RBCC family Q86XT4
Zinc finger protein RFP (TRIM27) TRIM/RBCC family P14373
E3 ubiquitin-protein ligase LNX (LNX1) . Q8TBB1
Transporter and channel
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nuclear RNA export factor 1 (NXF1) NXF family Q9UBU9
RNA-binding protein with serine-rich domain 1 (RNPS1) Splicing factor SR family Q15287
Serine/arginine repetitive matrix protein 1 (SRRM1) Splicing factor SR family Q8IYB3
Kelch-like protein 2 (KLHL2) . O95198
Syntenin-1 (SDCBP) . O00560
Transcription factor
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger and SCAN domain-containing protein 21 (ZSCAN21) Krueppel C2H2-type zinc-finger protein family Q9Y5A6
Zinc finger protein 136 (ZNF136) Krueppel C2H2-type zinc-finger protein family P52737
Zinc finger protein 263 (ZNF263) Krueppel C2H2-type zinc-finger protein family O14978
Zinc finger protein 317 (ZNF317) Krueppel C2H2-type zinc-finger protein family Q96PQ6
Zinc finger protein 394 (ZNF394) Krueppel C2H2-type zinc-finger protein family Q53GI3
Zinc finger protein 398 (ZNF398) Krueppel C2H2-type zinc-finger protein family Q8TD17
Zinc finger protein 436 (ZNF436) Krueppel C2H2-type zinc-finger protein family Q9C0F3
Zinc finger protein 440 (ZNF440) Krueppel C2H2-type zinc-finger protein family Q8IYI8
Zinc finger protein 473 (ZNF473) Krueppel C2H2-type zinc-finger protein family Q8WTR7
Zinc finger protein 491 (ZNF491) Krueppel C2H2-type zinc-finger protein family Q8N8L2
Zinc finger protein 558 (ZNF558) Krueppel C2H2-type zinc-finger protein family Q96NG5
Zinc finger protein 764 (ZNF764) Krueppel C2H2-type zinc-finger protein family Q96H86
Zinc finger protein 768 (ZNF768) Krueppel C2H2-type zinc-finger protein family Q9H5H4
Zinc finger protein 837 (ZNF837) Krueppel C2H2-type zinc-finger protein family Q96EG3
Other
Click To Hide/Show 16 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Splicing factor Cactin (CACTIN) CACTIN family Q8WUQ7
DNA damage-inducible transcript 4-like protein (DDIT4L) DDIT4 family Q96D03
Sperm protamine P1 (PRM1) Protamine P1 family P04553
Pre-mRNA-splicing factor 38A (PRPF38A) PRP38 family Q8NAV1
Cleavage and polyadenylation specificity factor subunit 7 (CPSF7) RRM CPSF6/7 family Q8N684
Arginine/serine-rich protein 1 (RSRP1) RSRP family Q9BUV0
CLK4-associating serine/arginine rich protein (CLASRP) Splicing factor SR family Q8N2M8
RNA-binding protein 39 (RBM39) Splicing factor SR family Q14498
Serine/arginine-rich splicing factor 3 (SRSF3) Splicing factor SR family P84103
Large ribosomal subunit protein uL4m (MRPL4) Universal ribosomal protein uL4 family Q9BYD3
Leucine zipper protein 4 (LUZP4) . Q9P127
Smad nuclear-interacting protein 1 (SNIP1) . Q8TAD8
Tether containing UBX domain for GLUT4 (ASPSCR1) . Q9BZE9
U1 small nuclear ribonucleoprotein 70 kDa (SNRNP70) . P08621
U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 (ZRSR2) . Q15696
YTH domain-containing protein 1 (YTHDC1) . Q96MU7

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010
Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ml315 Small molecular drug D0UI7U
Pmid23642479c17 Small molecular drug D06CXU
Patented
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tg003 Small molecular drug D06MBI

References

1 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
4 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
5 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840