Protein:CDKL5 |
Protein Summary |
 Gene summary |
| Gene name: CDKL5 | ASpdb.0 ID: 6792 | Gene | Gene symbol | CDKL5 | Gene ID | 6792 |
| Gene name | cyclin dependent kinase like 5 |
| Synonyms | CFAP247|DEE2|EIEE2|ISSX|STK9 |
| Cytomap | Xp22.13 |
| Type of gene | protein-coding |
| Description | cyclin-dependent kinase-like 5cyclin dependent kinase 5 transcriptserine/threonine kinase 9serine/threonine-protein kinase 9 |
| Modification date | 20240415 |
| UniProtAcc | O76039 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CDKL5 | GO:0004672 | protein kinase activity | 16935860 |
| Gene | CDKL5 | GO:0005524 | ATP binding | 16935860 |
| Gene | CDKL5 | GO:0005634 | nucleus | 16935860 |
| Gene | CDKL5 | GO:0005654 | nucleoplasm | - |
| Gene | CDKL5 | GO:0005813 | centrosome | 29420175 |
| Gene | CDKL5 | GO:0016301 | kinase activity | 15917271 |
| Gene | CDKL5 | GO:0036064 | ciliary basal body | 29420175 |
| Gene | CDKL5 | GO:0046777 | protein autophosphorylation | 16935860 |
| Gene | CDKL5 | GO:0050804 | modulation of chemical synaptic transmission | 22922712 |
| Gene | CDKL5 | GO:0097542 | ciliary tip | 29420175 |
| Gene | CDKL5 | GO:0098978 | glutamatergic synapse | 22922712 |
| Gene | CDKL5 | GO:0099175 | regulation of postsynapse organization | 22922712 |
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 |
| O76039-2 | O76039-2_4bgq_A.pdb | 4BGQ | X-ray | 2.0 | A | 9 | 302 |
| 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 |
| O76039 | CDKL5 | O76039-2 | O76039-1 | 960 | 1030 | 905 | 960 | Substitution | GQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL | DGGCDGRRQRHHSGPQDRRFMLRTTEQQGEYFCCGDPKKPHTPCVPNRALHRPISSPAPYPVLQVRGTSMCPTLQVRGTDAFSCPTQQSGFSFFVRHVMREALIHRAQVNQAALLTYHENAALTGK | 905 | 1030 |
| Multiple sequence alignment of our canonical and alternatively spliced CDKL5 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CDKL5 |
| UniProt-id | ENSG | ENST | ENSP |
| O76039-2 | ENSG00000008086.13 | ENST00000623535.2 | ENSP00000485244.1 |
| O76039-1 | ENSG00000008086.13 | ENST00000379989.6 | ENSP00000369325.3 |
| O76039-1 | ENSG00000008086.13 | ENST00000379996.7 | ENSP00000369332.3 |
| UniProt-id | NM ID | NP ID |
| O76039-2 | NM_001323289.1 | NP_001310218.1 |
| O76039-1 | NM_001037343.1 | NP_001032420.1 |
| O76039-1 | NM_003159.2 | NP_003150.1 |
| Amino acid sequences of our canonical and alternatively spliced CDKL5 |
| accession_id | Protein sequence |
| O76039-2 | MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFE YVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSP ELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVL LDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGL PANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMES SQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRT LLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLS IGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPS PRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHS ASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPA |
| O76039-1 | MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFE YVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSP ELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVL LDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGL PANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMES SQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRT LLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLS IGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPS PRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHS ASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPA LQLPDGGCDGRRQRHHSGPQDRRFMLRTTEQQGEYFCCGDPKKPHTPCVPNRALHRPISSPAPYPVLQVRGTSMCPTLQVRGTDAFSCPT |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CDKL5 (go to UniProt):O76039 |
| 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 |
| O76039 | Region | 848 | 960 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=905;End=960 |
| O76039 | Compositional bias | 912 | 952 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=905;End=960 |
Gene Isoform Structures and Expression Levels for CDKL5 |
| Gene structures of our canonical and alternative spliced genes of CDKL5 * 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 O76039-2 |
| 3D view using mol* of O76039-1 |
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 O76039-2 |
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| pLDDT distribution across the protein length of O76039-1 |
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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 O76039-2 |
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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 |
| O76039-2 | 1.061 | 122 | 0.895 | 261.709 | 0.534 | 0.789 | 1.013 | 0.13 | 1.591 | 0.082 | 0.28 | 59,134,135,136,137,155,156,158,166,167,168,169,170 ,171,173,174,175,176,177,178,182,185,192,193,196,2 15,216,243,244,247 |
| O76039-1 | 1.026 | 384 | 1.066 | 1090.74 | 0.646 | 0.693 | 0.811 | 0.601 | 0.888 | 0.676 | 0.859 | 18,19,21,24,27,40,42,60,64,73,89,90,91,92,93,94,95 ,97,98,100,101,104,137,138,139,142,152,153,154,171 ,173,174,175,176,177,207,208,209,210,211,212,213,2 14,218,222,225,226,261,605,606,607,608,609,610,611 ,612,613,614,615,616,617,998,999,1001,1002,1003,10 05,1006,1007,1009,1010 |
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 O76039-2_O76039-2_4bgq_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 O76039-2_4bgq_A_O76039-1.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O76039-2_O76039-1.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O76039-2_vs_O76039-1.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O76039-2_vs_O76039-1.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 CDKL5 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to CDKL5 |
| Previous studies relating to the alternative splicing of CDKL5 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CDKL5 | 19740913 | CDKL5 influences RNA splicing activity by its association to the nuclear speckle molecular machinery. | Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause severe neurodevelopmental disorders including infantile spasms, encephalopathy, West-syndrome and an early-onset variant of Rett syndrome. CDKL5 is a serine/threonine kinase whose involvement in Rett syndrome can be inferred by its ability to directly bind and mediate phosphorylation of MeCP2. However, it remains to be elucidated how CDKL5 exerts its function. Here, we report that CDKL5 localizes to specific nuclear foci referred to as nuclear speckles in both cell lines and tissues. These sub-nuclear structures are traditionally considered as storage/modification sites of pre-mRNA splicing factors. Interestingly, we provide evidence that CDKL5 regulates the dynamic behaviour of nuclear speckles. Indeed, CDKL5 overexpression leads to nuclear speckle disassembly, and this event is strictly dependent on its kinase activity. Conversely, its down-regulation affects nuclear speckle morphology leading to abnormally large and uneven speckles. Similar results were obtained for primary adult fibroblasts isolated from CDKL5-mutated patients. Altogether, these findings indicate that CDKL5 controls nuclear speckle morphology probably by regulating the phosphorylation state of splicing regulatory proteins. Nuclear speckles are dynamic sites that can continuously supply splicing factors to active transcription sites, where splicing occurs. Notably, we proved that CDKL5 influences alternative splicing, at least as proved in heterologous minigene assays. In conclusion, we provide evidence that CDKL5 is involved indirectly in pre-mRNA processing, by controlling splicing factor dynamics. These findings identify a biological process whose disregulation might affect neuronal maturation and activity in CDKL5-related disorders. | D015518 | Rett Syndrome |
Clinically important variants in CDKL5 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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