Q86V97 · KBTB6_HUMAN
- ProteinKelch repeat and BTB domain-containing protein 6
- GeneKBTBD6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids674 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions as a substrate adapter for the RAC1 guanine exchange factor (GEF) TIAM1, mediating its 'Lys-48' ubiquitination and proteasomal degradation (PubMed:25684205).
By controlling this ubiquitination, regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205).
Ubiquitination of TIAM1 requires the membrane-associated protein GABARAP which may restrict locally the activity of the complex (PubMed:25684205).
By controlling this ubiquitination, regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205).
Ubiquitination of TIAM1 requires the membrane-associated protein GABARAP which may restrict locally the activity of the complex (PubMed:25684205).
Pathway
Protein modification; protein ubiquitination.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | Cul3-RING ubiquitin ligase complex | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Biological Process | negative regulation of signal transduction | |
Biological Process | proteasome-mediated ubiquitin-dependent protein catabolic process | |
Biological Process | protein K48-linked ubiquitination | |
Biological Process | regulation of Rac protein signal transduction | |
Biological Process | response to unfolded protein |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameKelch repeat and BTB domain-containing protein 6
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ86V97
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 99 | Loss of interaction with CUL3. Loss of function in TIAM1 ubiquitination and degradation. | ||||
Sequence: M → A | ||||||
Mutagenesis | 668 | Decreased interaction with GABARAP and GABARAPL2. Loss of function in TIAM1 ubiquitination and degradation. No effect on assembly of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex. | ||||
Sequence: W → A | ||||||
Mutagenesis | 668-671 | Decreased interaction with GABARAP and GABARAPL2. Loss of function in TIAM1 ubiquitination and degradation. No effect on assembly of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex. | ||||
Sequence: WVRV → AVRA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 583 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000119084 | 1-674 | Kelch repeat and BTB domain-containing protein 6 | |||
Sequence: MQSREDAPRSRRLASPRGGKRPKKIHKPTVSAFFTGPEELKDTAHSAALLAQLKSFYDARLLCDVTIEVVTPGSGPGTGRLFPCNRNVLAAACPYFKSMFTGGMYESQQASVTMHDVDAESFEVLVDYCYTGRVSLSEANVERLYAASDMLQLEYVREACASFLARRLDLTNCTAILKFADAFGHRKLRSQAQSYIAQNFKQLSHMGSIREETLADLTLAQLLAVLRLDSLDVESEQTVCHVAVQWLEAAPKERGPSAAEVFKCVRWMHFTEEDQDYLEGLLTKPIVKKYCLDVIEGALQMRYGDLLYKSLVPVPNSSSSSSSSNSLVSAAENPPQRLGMCAKEMVIFFGHPRDPFLCCDPYSGDLYKVPSPLTCLAHTRTVTTLAVCISPDHDIYLAAQPRTDLWVYKPAQNSWQQLADRLLCREGMDVAYLNGYIYILGGRDPITGVKLKEVECYNVKRNQWALVAPLPHSFLSFDLMVIRDYLYALNSKRMFCYDPSHNMWLKCVSLKRNDFQEACVFNEEIYCICDIPVMKVYNPVRAEWRQMNNIPLVSETNNYRIIKHGQKLLLITSRTPQWKKNRVTVYEYDIRGDQWINIGTTLGLLQFDSNFFCLSARVYPSCLEPGQSFLTEEEEIPSESSTEWDLGGFSEPDSESGSSSSLSDDDFWVRVAPQ |
Proteomic databases
PTM databases
Interaction
Subunit
Core component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205).
Interacts with GABARAP; the interaction is direct and is required for the ubiquitination of TIAM1 (PubMed:25684205).
Interacts with GABARAPL1, GABARAPL2 and MAP1LC3B; the interaction is direct (PubMed:25684205).
Interacts with GABARAP; the interaction is direct and is required for the ubiquitination of TIAM1 (PubMed:25684205).
Interacts with GABARAPL1, GABARAPL2 and MAP1LC3B; the interaction is direct (PubMed:25684205).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q86V97 | GABARAP O95166 | 3 | EBI-2514778, EBI-712001 | |
BINARY | Q86V97 | GABARAPL1 Q9H0R8 | 4 | EBI-2514778, EBI-746969 | |
BINARY | Q86V97 | GABARAPL2 P60520 | 2 | EBI-2514778, EBI-720116 | |
BINARY | Q86V97 | MAP1LC3B Q9GZQ8 | 2 | EBI-2514778, EBI-373144 | |
BINARY | Q86V97 | MAP1LC3C Q9BXW4 | 2 | EBI-2514778, EBI-2603996 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, repeat, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-28 | Disordered | ||||
Sequence: MQSREDAPRSRRLASPRGGKRPKKIHKP | ||||||
Domain | 63-138 | BTB | ||||
Sequence: CDVTIEVVTPGSGPGTGRLFPCNRNVLAAACPYFKSMFTGGMYESQQASVTMHDVDAESFEVLVDYCYTGRVSLSE | ||||||
Repeat | 386-435 | Kelch 1 | ||||
Sequence: AVCISPDHDIYLAAQPRTDLWVYKPAQNSWQQLADRLLCREGMDVAYLNG | ||||||
Repeat | 436-484 | Kelch 2 | ||||
Sequence: YIYILGGRDPITGVKLKEVECYNVKRNQWALVAPLPHSFLSFDLMVIRD | ||||||
Repeat | 486-523 | Kelch 3 | ||||
Sequence: LYALNSKRMFCYDPSHNMWLKCVSLKRNDFQEACVFNE | ||||||
Repeat | 524-564 | Kelch 4 | ||||
Sequence: EIYCICDIPVMKVYNPVRAEWRQMNNIPLVSETNNYRIIKH | ||||||
Repeat | 567-616 | Kelch 5 | ||||
Sequence: KLLLITSRTPQWKKNRVTVYEYDIRGDQWINIGTTLGLLQFDSNFFCLSA | ||||||
Region | 631-674 | Disordered | ||||
Sequence: TEEEEIPSESSTEWDLGGFSEPDSESGSSSSLSDDDFWVRVAPQ | ||||||
Repeat | 642-673 | Kelch 6 | ||||
Sequence: TEWDLGGFSEPDSESGSSSSLSDDDFWVRVAP | ||||||
Compositional bias | 643-665 | Polar residues | ||||
Sequence: EWDLGGFSEPDSESGSSSSLSDD | ||||||
Motif | 668-671 | ATG8 interaction motif (AIM) | ||||
Sequence: WVRV |
Domain
The ATG8 interaction motif (AIM) mediates interaction with proteins of the ATG8 family including GABARAP.
The BTB domain is required for interaction with CUL3.
The Kelch repeats mediate interaction with TIAM1, a CUL3(KBTBD6/7) E3 ubiquitin ligase substrate.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length674
- Mass (Da)76,138
- Last updated2003-06-01 v1
- Checksum5ED49AAEC6350CB5
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 61 | in Ref. 1; BAB71238 | ||||
Sequence: L → Q | ||||||
Compositional bias | 643-665 | Polar residues | ||||
Sequence: EWDLGGFSEPDSESGSSSSLSDD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK056633 EMBL· GenBank· DDBJ | BAB71238.1 EMBL· GenBank· DDBJ | mRNA | ||
AK096608 EMBL· GenBank· DDBJ | BAC04826.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AL354696 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC000560 EMBL· GenBank· DDBJ | AAH00560.1 EMBL· GenBank· DDBJ | mRNA | ||
BC051349 EMBL· GenBank· DDBJ | AAH51349.1 EMBL· GenBank· DDBJ | mRNA | ||
AL833839 EMBL· GenBank· DDBJ | CAD38699.1 EMBL· GenBank· DDBJ | mRNA |