KLHL20

The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 44-56 amino acid repeat motif. The kelch motif appears in many different polypeptide contexts and contains multiple potential protein-protein contact sites. Members of this family are present both throughout the cell and extracellularly, with diverse activities.

Full Name

Kelch Like Family Member 20

Function

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (PubMed:20389280).
The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination (PubMed:24768539).
Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking (PubMed:24768539).
Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (PubMed:21670212).
In case of tumor, the BCR(KLHL20) E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20)complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression (PubMed:21840486).

Biological Process

Cytoskeleton organizationManual Assertion Based On ExperimentTAS:ProtInc
Golgi to endosome transportManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Protein K33-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein transportIEA:UniProtKB-KW
Protein ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Response to interferon-alphaManual Assertion Based On ExperimentTAS:UniProtKB

Cellular Location

Cytoplasm, perinuclear region; Nucleus; Golgi apparatus, trans-Golgi network; Cell projection, axon; Cell projection, dendrite. Localizes in the perinuclear region in normal conditions. Following IFN-alpha or IFN-gamma treatment, it is relocalized and sequestrated to the PML nuclear bodies, preventing DAPK1 ubiquitination (PubMed:20389280).