BTRC
BTRC is a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. BTRC belongs to the Fbws class; in addition to an F-box, it contains multiple WD-40 repeats. BTRC mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B.
Function
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. Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996, PubMed:22087322).
SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959).
SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14681206, PubMed:14603323).
SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:10066435, PubMed:10497169, PubMed:10644755).
Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435).
SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25704143, PubMed:25503564).
SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity).
Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222).
May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3 (PubMed:16371461).
Mediates ubiquitination of REST, thereby leading to its proteasomal degradation (PubMed:21258371, PubMed:18354482).
Biological Process
Branching involved in mammary gland duct morphogenesis Source: Ensembl
Cellular response to organic cyclic compound Source: Ensembl
Fc-epsilon receptor signaling pathway Source: Reactome
G2/M transition of mitotic cell cycle Source: Reactome
Interleukin-1-mediated signaling pathway Source: Reactome
Mammary gland epithelial cell proliferation Source: Ensembl
Negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
Negative regulation of smoothened signaling pathway Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
NIK/NF-kappaB signaling Source: Reactome
Positive regulation of circadian rhythm Source: UniProtKB
Positive regulation of proteolysis Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of ubiquitin protein ligase activity Source: ParkinsonsUK-UCL
Post-translational protein modification Source: Reactome
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein dephosphorylation Source: UniProtKB
Protein destabilization Source: UniProtKB
Protein K48-linked ubiquitination Source: Ensembl
Protein polyubiquitination Source: ParkinsonsUK-UCL
Protein ubiquitination Source: UniProtKB
Regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
Regulation of circadian rhythm Source: UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
Regulation of mitotic cell cycle phase transition Source: Reactome
Regulation of proteasomal protein catabolic process Source: Ensembl
Rhythmic process Source: UniProtKB-KW
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Signal transduction Source: ProtInc
Stimulatory C-type lectin receptor signaling pathway Source: Reactome
Stress-activated MAPK cascade Source: Reactome
T cell receptor signaling pathway Source: Reactome
Ubiquitin-dependent protein catabolic process Source: UniProtKB
Viral process Source: UniProtKB-KW
Wnt signaling pathway Source: Reactome
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Datasheet