Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5B2EO)

• DTT Name: S-phase kinase-associated protein 2 (SKP2)
• 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
• Gene Name: SKP2
• DTT Type: Literature-reported target; [1]
• UniProt ID: SKP2_HUMAN
• TTD ID: T80306
• Sequence:
  MHRKHLQEIPDLSSNVATSFTWGWDSSKTSELLSGMGVSALEKEEPDSENIPQELLSNLG
  HPESPPRKRLKSKGSDKDFVIVRRPKLNRENFPGVSWDSLPDELLLGIFSCLCLPELLKV
  SGVCKRWYRLASDESLWQTLDLTGKNLHPDVTGRLLSQGVIAFRCPRSFMDQPLAEHFSP
  FRVQHMDLSNSVIEVSTLHGILSQCSKLQNLSLEGLRLSDPIVNTLAKNSNLVRLNLSGC
  SGFSEFALQTLLSSCSRLDELNLSWCFDFTEKHVQVAVAHVSETITQLNLSGYRKNLQKS
  DLSTLVRRCPNLVHLDLSDSVMLKNDCFQEFFQLNYLQHLSLSRCYDIIPETLLELGEIP
  TLKTLQVFGIVPDGTLQLLKEALPHLQINCSHFTTIARPTIGNKKNQEIWGIKCRLTLQK
  PSCL
• 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.
• KEGG Pathway:
  FoxO signaling pathway (hsa04068)
  Cell cycle (hsa04110)
  Ubiquitin mediated proteolysis (hsa04120)
  mTOR signaling pathway (hsa04150)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Small cell lung cancer (hsa05222)
• Reactome Pathway:
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  Ub-specific processing proteases (R-HSA-5689880)
  Orc1 removal from chromatin (R-HSA-68949)
  Cyclin D associated events in G1 (R-HSA-69231)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  Neddylation (R-HSA-8951664)
  Aberrant regulation of mitotic exit in cancer due to RB1 defects (R-HSA-9687136)
  Regulation of BACH1 activity (R-HSA-9708530)
  Antigen processing (R-HSA-983168)
  APC/C (R-HSA-174178)
• BioCyc Pathway: MetaCyc:ENSG00000145604-MON

References

• [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.