Protein:CLK2 |
Protein Summary |
 Gene summary |
| Gene name: CLK2 | ASpdb.0 ID: 1196 | Gene | Gene symbol | CLK2 | Gene ID | 1196 |
| Gene name | CDC like kinase 2 |
| Synonyms | - |
| Cytomap | 1q22 |
| Type of gene | protein-coding |
| Description | dual specificity protein kinase CLK2CLK kinase |
| Modification date | 20240407 |
| UniProtAcc | P49760 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CLK2 | GO:0004674 | protein serine/threonine kinase activity | 10480872 |
| Gene | CLK2 | GO:0005634 | nucleus | 9637771|28289210 |
| Gene | CLK2 | GO:0005654 | nucleoplasm | - |
| Gene | CLK2 | GO:0006468 | protein phosphorylation | 9637771|20682768|28289210 |
| Gene | CLK2 | GO:0016604 | nuclear body | - |
| Gene | CLK2 | GO:0043484 | regulation of RNA splicing | 9637771 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P49760-1 | P49760-1_6fyk_A.pdb | 6FYK | X-ray | 2.39 | A | 137 | 485 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P49760 | CLK2 | P49760-1 | P49760-2 | 499 | 139 | 134 | 139 | Substitution | QHSSRR | MKSLAP | 134 | 139 |
| P49760 | CLK2 | P49760-1 | P49760-2 | 499 | 139 | 140 | 499 | Deletion | none | none | 139 | 139 |
| P49760 | CLK2 | P49760-1 | P49760-3 | 499 | 498 | 134 | 134 | Deletion | none | none | 133 | 133 |
| Multiple sequence alignment of our canonical and alternatively spliced CLK2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CLK2 |
| UniProt-id | ENSG | ENST | ENSP |
| P49760-1 | ENSG00000176444.19 | ENST00000368361.9 | ENSP00000357345.4 |
| P49760-1 | ENSG00000261893.5 | ENST00000574445.5 | ENSP00000460443.1 |
| P49760-3 | ENSG00000176444.19 | ENST00000361168.9 | ENSP00000354856.5 |
| P49760-3 | ENSG00000261893.5 | ENST00000572269.5 | ENSP00000459461.1 |
| UniProt-id | NM ID | NP ID |
| P49760-1 | NM_001294338.1 | NP_001281267.1 |
| P49760-3 | NM_003993.3 | NP_003984.2 |
| Amino acid sequences of our canonical and alternatively spliced CLK2 |
| accession_id | Protein sequence |
| P49760-1 | MPHPRRYHSSERGSRGSYREHYRSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYDDRSSDRRVYDRRYCGSYRRNDYSRDRGDAY YDTDYRHSYEYQRENSSYRSQRSSRRKHRRRRRRSRTFSRSSSQHSSRRAKSVEDDAEGHLIYHVGDWLQERYEIVSTLGEGTFGRVVQC VDHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPDNKNLCVQMFDWFDYHGHMCISFELLGLSTFDFLKDNNYLPYPIHQVRHM AFQLCQAVKFLHDNKLTHTDLKPENILFVNSDYELTYNLEKKRDERSVKSTAVRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQ PCDVWSIGCIIFEYYVGFTLFQTHDNREHLAMMERILGPIPSRMIRKTRKQKYFYRGRLDWDENTSAGRYVRENCKPLRRYLTSEAEEHH |
| P49760-2 | MPHPRRYHSSERGSRGSYREHYRSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYDDRSSDRRVYDRRYCGSYRRNDYSRDRGDAY |
| P49760-3 | MPHPRRYHSSERGSRGSYREHYRSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYDDRSSDRRVYDRRYCGSYRRNDYSRDRGDAY YDTDYRHSYEYQRENSSYRSQRSSRRKHRRRRRRSRTFSRSSSHSSRRAKSVEDDAEGHLIYHVGDWLQERYEIVSTLGEGTFGRVVQCV DHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPDNKNLCVQMFDWFDYHGHMCISFELLGLSTFDFLKDNNYLPYPIHQVRHMA FQLCQAVKFLHDNKLTHTDLKPENILFVNSDYELTYNLEKKRDERSVKSTAVRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQP CDVWSIGCIIFEYYVGFTLFQTHDNREHLAMMERILGPIPSRMIRKTRKQKYFYRGRLDWDENTSAGRYVRENCKPLRRYLTSEAEEHHQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CLK2 (go to UniProt):P49760 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P49760 | Domain | 163 | 479 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=140;End=499 |
| P49760 | Region | 101 | 143 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=134;End=139 |
| P49760 | Region | 101 | 143 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=140;End=499 |
| P49760 | Region | 101 | 143 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=134;End=134 |
Gene Isoform Structures and Expression Levels for CLK2 |
| Gene structures of our canonical and alternative spliced genes of CLK2 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P49760-1 |
| 3D view using mol* of P49760-2 |
| 3D view using mol* of P49760-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P49760-1 |
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| pLDDT distribution across the protein length of P49760-2 |
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| pLDDT distribution across the protein length of P49760-3 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P49760-1 |
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| Ramachandran plot of P49760-2 |
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| Ramachandran plot of P49760-3 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P49760-1 | 1.034 | 204 | 1.062 | 668.85 | 0.56 | 0.726 | 0.941 | 0.626 | 0.962 | 0.65 | 1.263 | 67,68,69,70,71,73,74,77,78,80,81,251,254,255,258,2 59,260,261,294,313,344,346,347,373,376,377,378,379 ,380,381,382,383,384,388,392,396,427,430,434,435,4 41 |
| P49760-2 | 0.425 | 16 | 0.334 | 24.01 | 0.768 | 0.496 | 0.761 | 0.144 | 1.043 | 0.138 | 0.383 | 96,97,98,99,100,101
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| P49760-3 | 1.062 | 183 | 1.113 | 640.038 | 0.631 | 0.72 | 0.855 | 0.908 | 0.795 | 1.142 | 1.164 | 168,169,170,171,173,174,176,190,191,192,194,203,20 6,207,209,210,211,226,242,243,244,245,246,247,248, 250,251,287,288,289,291,293,294,296,325,326,327,32 8,329,330,331,332,335,336,337,338,341,342,357 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P49760-1_P49760-1_6fyk_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P49760-1_6fyk_A_P49760-2.pdb |
| 3D view using mol* of P49760-1_6fyk_A_P49760-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P49760-1_P49760-2.pdb |
| 3D view using mol* of P49760-1_P49760-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P49760-1_vs_P49760-2.png |
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| ./stats/secondary_structure/figure/P49760-1_vs_P49760-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P49760-1_vs_P49760-2.png |
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| ./stats/relative_asa/P49760-1_vs_P49760-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CLK2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P49760 | CLK2 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
Related Diseases to CLK2 |
| Previous studies relating to the alternative splicing of CLK2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CLK2 | 9852100 | The cellular localization of the murine serine/arginine-rich protein kinase CLK2 is regulated by serine 141 autophosphorylation. | Pre-mRNA splicing is catalyzed by a multitude of proteins including serine/arginine-rich (SR) proteins, which are thought to play a crucial role in the formation of spliceosomes and in the regulation of alternative splicing. SR proteins are highly phosphorylated, and their kinases are believed to regulate the recruitment of SR proteins from nuclear storage compartments known as speckles. Recently, a family of autophosphorylating kinases termed CLK (CDC2/CDC28-like kinases) was shown to phosphorylate SR proteins and to influence alternative splicing in overexpression systems. Here we used endogenous CLK2 protein to demonstrate that it displays different biochemical characteristics compared with its overexpressed protein and that it is differentially phosphorylated in vivo. Furthermore, CLK2 changed its nuclear localization upon treatment with the kinase inhibitor 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole. We have also identified a CLK2 autophosphorylation site, which is highly conserved among all CLK proteins, and we show by site-directed mutagenesis that its phosphorylation influences the subnuclear localization of CLK2. Our data suggest that CLK2 localization and possibly activity are influenced by a balance of CLK2 autophosphorylation and the regulation by CLK2 kinases and phosphatases. | D004915 | Leukemia, Erythroblastic, Acute |
Clinically important variants in CLK2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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