SKP2
Summary: This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| S-phase kinase associated protein 2 | MIM:601436 | Ensembl:ENSG00000145604 | HGNC:HGNC:10901 | PA35801 | 5p13.2 |
Gene Categories:
TUMOR SUPPRESSORGO terms in SKP2
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| BP | IEA | GO:0000082 | G1/S transition of mitotic cell cycle |
| BP | IBA | GO:0000086 | G2/M transition of mitotic cell cycle |
| BP | IEA | GO:0000086 | G2/M transition of mitotic cell cycle |
| BP | TAS | GO:0000209 | protein polyubiquitination |
| BP | IEA | GO:0006511 | ubiquitin-dependent protein catabolic process |
| BP | TAS | GO:0008283 | cell proliferation |
| BP | TAS | GO:0016579 | protein deubiquitination |
| BP | IBA | GO:0031146 | SCF-dependent proteasomal ubiquitin-dependent protein catabolic process |
| BP | IEA | GO:0033148 | positive regulation of intracellular estrogen receptor signaling pathway |
| BP | IDA | GO:0042981 | regulation of apoptotic process |
| BP | TAS | GO:0043687 | post-translational protein modification |
| BP | IEA | GO:0048661 | positive regulation of smooth muscle cell proliferation |
| BP | IBA | GO:0051726 | regulation of cell cycle |
| BP | IEA | GO:0051726 | regulation of cell cycle |
| BP | IEA | GO:0071460 | cellular response to cell-matrix adhesion |
| BP | IEA | GO:1902916 | positive regulation of protein polyubiquitination |
| CC | IBA | GO:0005634 | nucleus |
| CC | IDA | GO:0005634 | nucleus |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | IDA | GO:0005730 | nucleolus |
| CC | IBA | GO:0005829 | cytosol |
| CC | IDA | GO:0005829 | cytosol |
| CC | TAS | GO:0005829 | cytosol |
| CC | IBA | GO:0019005 | SCF ubiquitin ligase complex |
| CC | IDA | GO:0019005 | SCF ubiquitin ligase complex |
| MF | EXP | GO:0004842 | ubiquitin-protein transferase activity |
| MF | TAS | GO:0004842 | ubiquitin-protein transferase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IBA | GO:0061630 | ubiquitin protein ligase activity |
| MF | IEA | GO:0061630 | ubiquitin protein ligase activity |
Gene expression in normal tissue: SKP2
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in SKP2
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| kegg | hsa04068 | FoxO signaling pathway - Homo sapiens (human) |
| kegg | hsa04110 | Cell cycle - Homo sapiens (human) |
| kegg | hsa04120 | Ubiquitin mediated proteolysis - Homo sapiens (human) |
| kegg | hsa04150 | mTOR signaling pathway - Homo sapiens (human) |
| kegg | hsa05168 | Herpes simplex infection - Homo sapiens (human) |
| kegg | hsa05169 | Epstein-Barr virus infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05203 | Viral carcinogenesis - Homo sapiens (human) |
| kegg | hsa05222 | Small cell lung cancer - Homo sapiens (human) |
| pid | foxm1pathway | FOXM1 transcription factor network |
| pid | foxopathway | FoxO family signaling |
| pid | myc_pathway | C-MYC pathway |
| pid | notch_pathway | Notch signaling pathway |
| pid | p53regulationpathway | p53 pathway |
| pid | rb_1pathway | Regulation of retinoblastoma protein |
| netpath | Pathway_Notch | Notch |
| wikipathways | WP179 | Cell Cycle |
| wikipathways | WP2446 | Retinoblastoma (RB) in Cancer |
| wikipathways | WP3640 | Imatinib and Chronic Myeloid Leukemia |
| reactome | R-HSA-1280218 | Adaptive Immune System |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins |
| reactome | R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 |
| reactome | R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-453276 | Regulation of mitotic cell cycle |
| reactome | R-HSA-453279 | Mitotic G1-G1/S phases |
| reactome | R-HSA-5688426 | Deubiquitination |
| reactome | R-HSA-5689880 | Ub-specific processing proteases |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-68949 | Orc1 removal from chromatin |
| reactome | R-HSA-69052 | Switching of origins to a post-replicative state |
| reactome | R-HSA-69202 | Cyclin E associated events during G1/S transition |
| reactome | R-HSA-69206 | G1/S Transition |
| reactome | R-HSA-69231 | Cyclin D associated events in G1 |
| reactome | R-HSA-69236 | G1 Phase |
| reactome | R-HSA-69239 | Synthesis of DNA |
| reactome | R-HSA-69242 | S Phase |
| reactome | R-HSA-69278 | Cell Cycle, Mitotic |
| reactome | R-HSA-69306 | DNA Replication |
| reactome | R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-8878166 | Transcriptional regulation by RUNX2 |
| reactome | R-HSA-8939902 | Regulation of RUNX2 expression and activity |
| reactome | R-HSA-8951664 | Neddylation |
| reactome | R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation |
| reactome | R-HSA-983169 | Class I MHC mediated antigen processing & presentation |
| biocarta | p27pathway | regulation of p27 phosphorylation during cell cycle progression |
| biocarta | skp2e2fpathway | e2f1 destruction pathway |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD483 | SCH-529074 | 1 |
| iGMDRD231 | Importazole | 2 |
| iGMDRD116 | CD437 | 2 |
| iGMDRD427 | ABT737 | 3 |
| iGMDRD387 | CHIR-99021 | 1 |
| iGMDRD126 | Tipifarnib | 3 |
| iGMDRD474 | Avrainvillamide | 3 |
| iGMDRD210 | AC55649 | 3 |
| iGMDRD886 | Compound 1541A | 6 |
| iGMDRD280 | CYTOCHALASIN B | 3 |
| iGMDRD577 | BIX01294 | 3 |
| iGMDRD399 | Selumetinib | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in SKP2
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