Target Information
| Target General Information | Top | |||||
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| Target ID |
T74839
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| Target Name |
Cyclin-dependent kinase 13 (CDK13)
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| Synonyms |
CDC2-related protein kinase 5; Cell division cycle 2-like protein kinase 5; Cell division protein kinase 13; hCDK13; Cholinesterase-related cell division controller
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| Gene Name |
CDK13
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.22
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| Sequence |
MPSSSDTALGGGGGLSWAEKKLEERRKRRRFLSPQQPPLLLPLLQPQLLQPPPPPPPLLF
LAAPGTAAAAAAAAAASSSCFSPGPPLEVKRLARGKRRAGGRQKRRRGPRAGQEAEKRRV FSLPQPQQDGGGGASSGGGVTPLVEYEDVSSQSEQGLLLGGASAATAATAAGGTGGSGGS PASSSGTQRRGEGSERRPRRDRRSSSGRSKERHREHRRRDGQRGGSEASKSRSRHSHSGE ERAEVAKSGSSSSSGGRRKSASATSSSSSSRKDRDSKAHRSRTKSSKEPPSAYKEPPKAY REDKTEPKAYRRRRSLSPLGGRDDSPVSHRASQSLRSRKSPSPAGGGSSPYSRRLPRSPS PYSRRRSPSYSRHSSYERGGDVSPSPYSSSSWRRSRSPYSPVLRRSGKSRSRSPYSSRHS RSRSRHRLSRSRSRHSSISPSTLTLKSSLAAELNKNKKARAAEAARAAEAAKAAEATKAA EAAAKAAKASNTSTPTKGNTETSASASQTNHVKDVKKIKIEHAPSPSSGGTLKNDKAKTK PPLQVTKVENNLIVDKATKKAVIVGKESKSAATKEESVSLKEKTKPLTPSIGAKEKEQHV ALVTSTLPPLPLPPMLPEDKEADSLRGNISVKAVKKEVEKKLRCLLADLPLPPELPGGDD LSKSPEEKKTATQLHSKRRPKICGPRYGETKEKDIDWGKRCVDKFDIIGIIGEGTYGQVY KARDKDTGEMVALKKVRLDNEKEGFPITAIREIKILRQLTHQSIINMKEIVTDKEDALDF KKDKGAFYLVFEYMDHDLMGLLESGLVHFNENHIKSFMRQLMEGLDYCHKKNFLHRDIKC SNILLNNRGQIKLADFGLARLYSSEESRPYTNKVITLWYRPPELLLGEERYTPAIDVWSC GCILGELFTKKPIFQANQELAQLELISRICGSPCPAVWPDVIKLPYFNTMKPKKQYRRKL REEFVFIPAAALDLFDYMLALDPSKRCTAEQALQCEFLRDVEPSKMPPPDLPLWQDCHEL WSKKRRRQKQMGMTDDVSTIKAPRKDLSLGLDDSRTNTPQGVLPSSQLKSQGSSNVAPVK TGPGQHLNHSELAILLNLLQSKTSVNMADFVQVLNIKVNSETQQQLNKINLPAGILATGE KQTDPSTPQQESSKPLGGIQPSSQTIQPKVETDAAQAAVQSAFAVLLTQLIKAQQSKQKD VLLEERENGSGHEASLQLRPPPEPSTPVSGQDDLIQHQDMRILELTPEPDRPRILPPDQR PPEPPEPPPVTEEDLDYRTENQHVPTTSSSLTDPHAGVKAALLQLLAQHQPQDDPKREGG IDYQAGDTYVSTSDYKDNFGSSSFSSAPYVSNDGLGSSSAPPLERRSFIGNSDIQSLDNY STASSHSGGPPQPSAFSESFPSSVAGYGDIYLNAGPMLFSGDKDHRFEYSHGPIAVLANS SDPSTGPESTHPLPAKMHNYNYGGNLQENPSGPSLMHGQTWTSPAQGPGYSQGYRGHIST STGRGRGRGLPY Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of human Cdk13/Cyclin K in complex with ADP-aluminum fluoride | PDB:5EFQ | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
IDWGKRCVDK
704 FDIIGIIGEG714 TYGQVYKARD724 KDTGEMVALK734 KVRLDNEKEG744 FPITAIREIK 754 ILRQLTHQSI764 INMKEIVTDK774 EGAFYLVFEY793 MDHDLMGLLE803 SGLVHFNENH 813 IKSFMRQLME823 GLDYCHKKNF833 LHRDIKCSNI843 LLNNRGQIKL853 ADFGLARLYS 863 SEESRPYNKV874 ITLWYRPPEL884 LLGEERYTPA894 IDVWSCGCIL904 GELFTKKPIF 914 QANQELAQLE924 LISRICGSPC934 PAVWPDVIKL944 PYFNTMKPKK954 QYRRKLREEF 964 VFIPAAALDL974 FDYMLALDPS984 KRCTAEQALQ994 CEFLRDVEPS1004 KMPPPDLPLW 1014 QDCHELWSKK1024 R
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ILE711
3.680
GLY712
3.991
GLU713
3.779
GLY714
3.133
THR715
3.086
VAL719
3.789
ALA732
3.412
LYS734
3.165
GLU752
4.902
ILE765
4.021
PHE791
3.654
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| Ligand Name: Phosphonothreonine | Ligand Info | |||||
| Structure Description | Crystal structure of human Cdk13/Cyclin K in complex with ADP-aluminum fluoride | PDB:5EFQ | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
IDWGKRCVDK
704 FDIIGIIGEG714 TYGQVYKARD724 KDTGEMVALK734 KVRLDNEKEG744 FPITAIREIK 754 ILRQLTHQSI764 INMKEIVTDK774 EGAFYLVFEY793 MDHDLMGLLE803 SGLVHFNENH 813 IKSFMRQLME823 GLDYCHKKNF833 LHRDIKCSNI843 LLNNRGQIKL853 ADFGLARLYS 863 SEESRPYNKV874 ITLWYRPPEL884 LLGEERYTPA894 IDVWSCGCIL904 GELFTKKPIF 914 QANQELAQLE924 LISRICGSPC934 PAVWPDVIKL944 PYFNTMKPKK954 QYRRKLREEF 964 VFIPAAALDL974 FDYMLALDPS984 KRCTAEQALQ994 CEFLRDVEPS1004 KMPPPDLPLW 1014 QDCHELWSKK1024 R
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.67E-01 | Radiality | 1.26E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 6.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nat Chem Biol. 2016 Oct;12(10):876-84. | |||||
| REF 2 | Structural and Functional Analysis of the Cdk13/Cyclin K Complex. Cell Rep. 2016 Jan 12;14(2):320-31. | |||||
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