Hmdb loader

Showing Protein DDB1- and CUL4-associated factor 15 (HMDBP13663)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP13663
Secondary Accession Numbers None
Name DDB1- and CUL4-associated factor 15
Synonyms Not Available
Gene Name DCAF15
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Substrate-recognition component of the DCX(DCAF15) complex, a cullin-4-RING E3 ubiquitin-protein ligase complex that mediates ubiquitination and degradation of target proteins (PubMed:16949367, PubMed:31452512). The DCX(DCAF15) complex acts as a regulator of the natural killer (NK) cells effector functions, possibly by mediating ubiquitination and degradation of cohesin subunits SMC1A and SMC3 (PubMed:31452512). May play a role in the activation of antigen-presenting cells (APC) and their interaction with NK cells (PubMed:31452512).Binding of aryl sulfonamide anticancer drugs, such as indisulam (E7070) or E7820, change the substrate specificity of the DCX(DCAF15) complex, leading to promote ubiquitination and degradation of splicing factor RBM39 (PubMed:28437394, PubMed:28302793, PubMed:31693891, PubMed:31452512). RBM39 degradation results in splicing defects and death in cancer cell lines (PubMed:28437394, PubMed:28302793, PubMed:31693891). Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactor RBM39 (PubMed:31686031, PubMed:31819272). Aryl sulfonamide anticancer drugs also promote ubiquitination and degradation of RBM23 and PRPF39 (PubMed:31693891, PubMed:31626998, PubMed:31686031).
Pathways
  • protein ubiquitination
Reactions Not Available
GO Classification
Biological Process
immune system process
protein ubiquitination
protein polyubiquitination
regulation of natural killer cell activation
Cellular Component
Cul4-RING E3 ubiquitin ligase complex
Molecular Function
metal ion binding
small molecule binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 600
Molecular Weight 66462.845
Theoretical pI 6.581
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q66K64
UniProtKB/Swiss-Prot Entry Name DCA15_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  10. Authors unspecified: Erratum for the Research Article "Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15" by T. Han, M. Goralski, N. Gaskill, E. Capota, J. Kim, T. C. Ting, Y. Xie, N. S. Williams, D. Nijhawan. Science. 2017 May 26;356(6340). pii: 356/6340/eaan7977. doi: 10.1126/science.aan7977. [PubMed:28546157 ]
  11. Ting TC, Goralski M, Klein K, Wang B, Kim J, Xie Y, Nijhawan D: Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15. Cell Rep. 2019 Nov 5;29(6):1499-1510.e6. doi: 10.1016/j.celrep.2019.09.079. [PubMed:31693891 ]
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  13. Jia X, Pan L, Zhu M, Hu H, Zhai L, Liu J, Hu M, Liu B, Tan M: pSILAC method coupled with two complementary digestion approaches reveals PRPF39 as a new E7070-dependent DCAF15 substrate. J Proteomics. 2020 Jan 6;210:103545. doi: 10.1016/j.jprot.2019.103545. Epub 2019 Oct 15. [PubMed:31626998 ]
  14. Faust TB, Yoon H, Nowak RP, Donovan KA, Li Z, Cai Q, Eleuteri NA, Zhang T, Gray NS, Fischer ES: Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat Chem Biol. 2020 Jan;16(1):7-14. doi: 10.1038/s41589-019-0378-3. Epub 2019 Nov 4. [PubMed:31686031 ]
  15. Bussiere DE, Xie L, Srinivas H, Shu W, Burke A, Be C, Zhao J, Godbole A, King D, Karki RG, Hornak V, Xu F, Cobb J, Carte N, Frank AO, Frommlet A, Graff P, Knapp M, Fazal A, Okram B, Jiang S, Michellys PY, Beckwith R, Voshol H, Wiesmann C, Solomon JM, Paulk J: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex. Nat Chem Biol. 2020 Jan;16(1):15-23. doi: 10.1038/s41589-019-0411-6. Epub 2019 Dec 9. [PubMed:31819272 ]
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