Q66K64 · DCA15_HUMAN
- ProteinDDB1- and CUL4-associated factor 15
- GeneDCAF15
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids600 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
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:28302793, PubMed:28437394, PubMed:31452512, PubMed:31693891).
RBM39 degradation results in splicing defects and death in cancer cell lines (PubMed:28302793, PubMed:28437394, 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:31626998, PubMed:31686031, PubMed:31693891).
RBM39 degradation results in splicing defects and death in cancer cell lines (PubMed:28302793, PubMed:28437394, 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:31626998, PubMed:31686031, PubMed:31693891).
Activity regulation
Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactors, such as RBM39.
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 193 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 196 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 211 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 214 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 231 | E7820 (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 234-235 | E7820 (UniProtKB | ChEBI) | ||||
Sequence: AF |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | Cul4-RING E3 ubiquitin ligase complex | |
Molecular Function | metal ion binding | |
Molecular Function | small molecule binding | |
Biological Process | immune system process | |
Biological Process | protein polyubiquitination | |
Biological Process | protein ubiquitination | |
Biological Process | regulation of natural killer cell activation |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDDB1- and CUL4-associated factor 15
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ66K64
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 90 | Abolished interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: V → D | ||||||
Mutagenesis | 91 | Abolished interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: L → P | ||||||
Mutagenesis | 112 | Abolished interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: W → R | ||||||
Mutagenesis | 129 | Abolished interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: F → S or V | ||||||
Mutagenesis | 182 | Decreased interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: V → D | ||||||
Mutagenesis | 196 | Decreased interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 232 | Decreased interaction with RBM39 in presence of indisulam, without affecting interaction with DDA1 and DDB1. | ||||
Sequence: Q → R | ||||||
Mutagenesis | 244 | Decreased interaction with DDB1, DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: L → P | ||||||
Mutagenesis | 392 | Decreased interaction with DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: L → P | ||||||
Mutagenesis | 420 | Decreased interaction with DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: T → P | ||||||
Mutagenesis | 444 | Decreased interaction with DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: E → K | ||||||
Mutagenesis | 453 | Decreased interaction with DDA1 and RBM39 in presence of indisulam. | ||||
Sequence: V → D | ||||||
Mutagenesis | 475 | Decreased interaction with RBM39 in presence of indisulam, without affecting interaction with DDA1 and DDB1. | ||||
Sequence: D → H, N, or V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,081 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000314485 | 1-600 | UniProt | DDB1- and CUL4-associated factor 15 | |||
Sequence: MAPSSKSERNSGAGSGGGGPGGAGGKRAAGRRREHVLKQLERVKISGQLSPRLFRKLPPRVCVSLKNIVDEDFLYAGHIFLGFSKCGRYVLSYTSSSGDDDFSFYIYHLYWWEFNVHSKLKLVRQVRLFQDEEIYSDLYLTVCEWPSDASKVIVFGFNTRSANGMLMNMMMMSDENHRDIYVSTVAVPPPGRCAACQDASRAHPGDPNAQCLRHGFMLHTKYQVVYPFPTFQPAFQLKKDQVVLLNTSYSLVACAVSVHSAGDRSFCQILYDHSTCPLAPASPPEPQSPELPPALPSFCPEAAPARSSGSPEPSPAIAKAKEFVADIFRRAKEAKGGVPEEARPALCPGPSGSRCRAHSEPLALCGETAPRDSPPASEAPASEPGYVNYTKLYYVLESGEGTEPEDELEDDKISLPFVVTDLRGRNLRPMRERTAVQGQYLTVEQLTLDFEYVINEVIRHDATWGHQFCSFSDYDIVILEVCPETNQVLINIGLLLLAFPSPTEEGQLRPKTYHTSLKVAWDLNTGIFETVSVGDLTEVKGQTSGSVWSSYRKSCVDMVMKWLVPESSGRYVNRMTNEALHKGCSLKVLADSERYTWIVL | |||||||
Modified residue (large scale data) | 11 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 50 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 50 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 308 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 310 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 310 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 314 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 314 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 359 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 368 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 373 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the DCX(DCAF15) complex, also named CLR4(DCAF15) complex, composed of DCAF15, DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q66K64 | RIPPLY1 Q0D2K3 | 3 | EBI-2559052, EBI-10226430 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-30 | Disordered | ||||
Sequence: MAPSSKSERNSGAGSGGGGPGGAGGKRAAG | ||||||
Compositional bias | 280-299 | Pro residues | ||||
Sequence: PASPPEPQSPELPPALPSFC | ||||||
Region | 280-316 | Disordered | ||||
Sequence: PASPPEPQSPELPPALPSFCPEAAPARSSGSPEPSPA |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length600
- Mass (Da)66,463
- Last updated2004-10-11 v1
- Checksum091BB2D0AADF3E6F
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 280-299 | Pro residues | ||||
Sequence: PASPPEPQSPELPPALPSFC |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK093072 EMBL· GenBank· DDBJ | BAG52648.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471106 EMBL· GenBank· DDBJ | EAW84386.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002926 EMBL· GenBank· DDBJ | AAH02926.2 EMBL· GenBank· DDBJ | mRNA | ||
BC013280 EMBL· GenBank· DDBJ | AAH13280.2 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
BC080575 EMBL· GenBank· DDBJ | AAH80575.1 EMBL· GenBank· DDBJ | mRNA |