Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6G10V)

• DTT Name: Vitiligo-associated protein 1 (FBXO11)
• Synonyms: Vitiligoassociated protein 1; VIT1; VIT-1; UG063H01; Protein arginine N-methyltransferase 9; PRMT9; Fbox only protein 11; FBX11; F-box only protein 11
• Gene Name: FBXO11
• DTT Type: Literature-reported target; [1]
• UniProt ID: FBX11_HUMAN
• TTD ID: T11203
• Sequence:
  MNSVRAANRRPRRVSRPRPVQQQQQQPPQQPPPQPPQQQPPQQQPPPPPQQQQQQQPPPP
  PPPPPPLPQERNNVGERDDDVPADMVAEESGPGAQNSPYQLRRKTLLPKRTACPTKNSME
  GASTSTTENFGHRAKRARVSGKSQDLSAAPAEQYLQEKLPDEVVLKIFSYLLEQDLCRAA
  CVCKRFSELANDPILWKRLYMEVFEYTRPMMHPEPGKFYQINPEEYEHPNPWKESFQQLY
  KGAHVKPGFAEHFYSNPARYKGRENMLYYDTIEDALGGVQEAHFDGLIFVHSGIYTDEWI
  YIESPITMIGAAPGKVADKVIIENTRDSTFVFMEGSEDAYVGYMTIRFNPDDKSAQHHNA
  HHCLEITVNCSPIIDHCIIRSTCTVGSAVCVSGQGACPTIKHCNISDCENVGLYITDHAQ
  GIYEDNEISNNALAGIWVKNHGNPIIRRNHIHHGRDVGVFTFDHGMGYFESCNIHRNRIA
  GFEVKAYANPTVVRCEIHHGQTGGIYVHEKGRGQFIENKIYANNFAGVWITSNSDPTIRG
  NSIFNGNQGGVYIFGDGRGLIEGNDIYGNALAGIQIRTNSCPIVRHNKIHDGQHGGIYVH
  EKGQGVIEENEVYSNTLAGVWVTTGSTPVLRRNRIHSGKQVGVYFYDNGHGVLEDNDIYN
  HMYSGVQIRTGSNPKIRRNKIWGGQNGGILVYNSGLGCIEDNEIFDNAMAGVWIKTDSNP
  TLRRNKIHDGRDGGICIFNGGRGLLEENDIFRNAQAGVLISTNSHPILRKNRIFDGFAAG
  IEITNHATATLEGNQIFNNRFGGLFLASGVNVTMKDNKIMNNQDAIEKAVSRGQCLYKIS
  SYTSYPMHDFYRCHTCNTTDRNAICVNCIKKCHQGHDVEFIRHDRFFCDCGAGTLSNPCT
  LAGEPTHDTDTLYDSAPPIESNTLQHN
• Function: The SCF(FBXO11) complex mediates ubiquitination and degradation of BCL6, thereby playing a role in the germinal center B-cells terminal differentiation toward memory B-cells and plasma cells. The SCF(FBXO11) complex also mediates ubiquitination and degradation of DTL, an important step for the regulation of TGF-beta signaling, cell migration and the timing of the cell-cycle progression and exit. Binds to and neddylates phosphorylated p53/TP53, inhibiting its transcriptional activity. SCF(FBXO11) does not seem to direct ubiquitination of p53/TP53. 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, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

References

• [1] FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012 Jan 5;481(7379):90-3.