FBXW11
TrCP2 (also known as Fbxw11 or HOS) is a protein that in humans is encoded by the BTRC (beta-transducin repeat containing) gene.
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 residue structural motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (Skp1-Cul1-F-box protein), which often, but not always, recognize substrates in a phosphorylation-dependent manner. F-box proteins are divided into 3 classes:
- Fbxws containing WD40 repeats,
- Fbxls containing leucine-rich repeats,
- and Fbxos containing either "other" protein-protein interaction modules or no recognizable motifs.
The protein encoded by FBXW11 belongs to the Fbxw class as, in addition to an F-box, this protein contains multiple WD40 repeats. This protein is homologous to  Xenopus TrCP, yeast Met30, Neurospora Scon2 and Drosophila Slimb. In mammals, in addition to TrCP2, a paralog protein (called TrCP1 or FBXW1) also exists, but, so far, their functions appear redundant and indistinguishable.

# Discovery
Human TrCP (referred to both TrCP1 and TrCP2) was originally identified as a cellular ubiquitin ligase that is bound by the HIV-1 Vpu viral protein to eliminate cellular CD4 by connecting it to the proteolytic machinery. Subsequently, TrCP was shown to regulate multiple cellular processes by mediating the degradation of various targets. Cell cycle regulators constitute a major group of TrCP substrates. During S phase, TrCP keeps CDK1 in check by promoting the degradation of the phosphatase CDC25A, whereas in G2, TrCP contributes to CDK1 activation by targeting the kinase WEE1 for degradation. In early mitosis, TrCP mediates the degradation of EMI1, an inhibitor of the APC/C ubiquitin ligase complex, which is responsible for the anaphase-metaphase transition (by inducing the proteolysis of Securin) and mitotic exit (by driving the degradation of mitotic CDK1 activating cyclin subunits). Furthermore, TrCP controls APC/C by targeting REST, thereby removing its transcriptional repression on MAD2, an essential component of the spindle assembly checkpoint that keeps APC/C inactive until all chromatids are attached to the spindle microtubles.

# Functions
TrCP plays important roles in regulating cell cycle checkpoints. In response to genotoxic stress, it contributes to turn off CDK1 activity by mediating the degradation of CDC25A in collaboration with Chk1, thereby preventing cell cycle progression before the completion of DNA repair. During recovery from DNA replication and DNA damage, TrCP instead targets Claspin in a Plk1-dependent manner.
TrCP has also emerged as an important player in protein translation, cell growth and survival. In response to mitogens, PDCD4, an inhibitor of the translation initiation factor eIF4A, is rapidly degraded in a TrCP- and S6K1-dependent manner, allowing efficient protein translation and cell growth. TrCP also cooperates with mTOR and CK1 to induce the degradation of DEPTOR (an mTOR inhibitor), thereby generating an auto-amplification loop to promote the full activation of mTOR. At the same time, TrCP mediates the degradation of the pro-apoptotic protein BimEL to promote cell survival.
TrCP also associates with phosphorylated IkappaBalpha and beta-catenin destruction motifs, probably functioning in multiple transcriptional programs by regulating the NF-kappaB and the WNT pathways.

# Interactions
BTRC (gene) has been shown to interact with:
- FBXW11
- DLG1
- IB
- NFKB2
- RELA
- SKP1A
- CDC34
- CUL1
- -catenin
- WEE1
- EMI1
- Cdc25A
- Claspin
- REST
- PDCD4
- DEPTOR

# Clinical Significance
TrCP behaves as an oncoprotein in some tissues. Elevated levels of TrCP expression have been found in colorectal, pancreatic, hapatoblastoma, and breast cancers.