Target Information
| Target General Information | Top | |||||
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| Target ID |
T80306
(Former ID: TTDR00814)
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| Target Name |
S-phase kinase-associated protein 2 (SKP2)
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| Synonyms |
Skp2; P45skp2; FBXL1; F-box/LRR-repeat protein 1; F-box protein Skp2; Cyclin-A/CDK2-associated protein p45; Cyclin A/CDK2-associated protein p45; Cyclin A/CDK2-associated p45
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| Gene Name |
SKP2
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| Target Type |
Literature-reported target
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| Function |
Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration. Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription.
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| UniProt ID | ||||||
| Sequence |
MHRKHLQEIPDLSSNVATSFTWGWDSSKTSELLSGMGVSALEKEEPDSENIPQELLSNLG
HPESPPRKRLKSKGSDKDFVIVRRPKLNRENFPGVSWDSLPDELLLGIFSCLCLPELLKV SGVCKRWYRLASDESLWQTLDLTGKNLHPDVTGRLLSQGVIAFRCPRSFMDQPLAEHFSP FRVQHMDLSNSVIEVSTLHGILSQCSKLQNLSLEGLRLSDPIVNTLAKNSNLVRLNLSGC SGFSEFALQTLLSSCSRLDELNLSWCFDFTEKHVQVAVAHVSETITQLNLSGYRKNLQKS DLSTLVRRCPNLVHLDLSDSVMLKNDCFQEFFQLNYLQHLSLSRCYDIIPETLLELGEIP TLKTLQVFGIVPDGTLQLLKEALPHLQINCSHFTTIARPTIGNKKNQEIWGIKCRLTLQK PSCL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T53FF1 | |||||
| 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: Benzamidine | Ligand Info | |||||
| Structure Description | Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide | PDB:2AST | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [2] |
| PDB Sequence |
VSWDSLPDEL
2104 LLGIFSCLCL2114 PELLKVSGVC2124 KRWYRLASDE2134 SLWQTLDLTG2144 KNLHPDVTGR 2154 LLSQGVIAFR2164 CPRSFMDQPL2174 AEHFSPFRVQ2184 HMDLSNSVIE2194 VSTLHGILSQ 2204 CSKLQNLSLE2214 GLRLSDPIVN2224 TLAKNSNLVR2234 LNLSGCSGFS2244 EFALQTLLSS 2254 CSRLDELNLS2264 WCFDFTEKHV2274 QVAVAHVSET2284 ITQLNLSGYR2294 KNLQKSDLST 2304 LVRRCPNLVH2314 LDLSDSVMLK2324 NDCFQEFFQL2334 NYLQHLSLSR2344 CYDIIPETLL 2354 ELGEIPTLKT2364 LQVFGIVPDG2374 TLQLLKEALP2384 HLQINCSHFT2394 TIARPTIGNK 2404 KNQEIWGIKC2414 RLTLQ
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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 Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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 Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| FoxO signaling pathway | hsa04068 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cell cycle | hsa04110 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Ubiquitin mediated proteolysis | hsa04120 | Affiliated Target |
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| Class: Genetic Information Processing => Folding, sorting and degradation | Pathway Hierarchy | ||
| mTOR signaling pathway | hsa04150 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 29 | Degree centrality | 3.12E-03 | Betweenness centrality | 1.09E-03 |
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| Closeness centrality | 2.56E-01 | Radiality | 1.44E+01 | Clustering coefficient | 3.00E-01 |
| Neighborhood connectivity | 6.24E+01 | Topological coefficient | 7.38E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas. Cancer Res. 2001 Oct 1;61(19):7044-7. | |||||
| REF 2 | Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005 Oct 7;20(1):9-19. | |||||
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