Recombinant E6AP(Q495-L852), HECT domain, E3 Ligase, E6-associated protein, UBE3A

The construct GGS_E6AP(Q495-L852) includes the catalytic HECT-domain spanning residues Q495-L852 comprising the C-lobe harboring the catalytic cysteine and the E2-binding site within the N-terminal lobe (N-lobe). The N-terminal GGS sequence remains from the TEV cleavage site.

Protein Construct: GGS_E6AP(Q495-L852)
Source: Human
Expression Host: Escherichia coli
Molecular weight [kDa]: 41.7
pI: 5.1
Extinction Coefficient [M^-1cm^-1]: 33350
Tag: none

Amino acid sequence:

QC Data: Datasheet
Purity SDS: >95 %
Hydrodynamic Radius (nm): 4.2
Polydispersity Index (PDI): 0.67
T_on (°C): 37.6
T_m (°C): 40.1

Structure and function

The E3 ligase E6AP belongs to the HECT (homologous to the E6AP C-terminus) family of E3 ligases, one of the three major classes of E3 ligases, alongside RING (really interesting new gene) and RBR (RING-between-RING) E3 ligases. The N-terminal region of full-length E6AP provides a platform for the binding of substrates targeted for ubiquitination, as well as regulatory proteins that modulate E6AP activity, such as the human papillomavirus (HPV) E6 protein and HERC2. In addition, many protein-protein interactions involving E6AP are mediated by an LxxLL motif (where x is any amino acid).
The C-terminal HECT domain adopts a characteristic L-shaped architecture comprising two distinct subdomains. It consists of a large N-lobe, which recruits E2-ubiquitin complexes, and a smaller C-lobe, which contains the catalytic cysteine responsible for the transfer of ubiquitin to lysine residues on the substrate.

E6AP as an important drug target

Several human diseases are associated with dysregulation of E6AP activity. The E3 ligase was first linked to cervical cancer when it was found to be hijacked by the HPV oncoprotein E6. Formation of the E6AP/E6 complex leads to the ubiquitination and subsequent degradation of the tumor suppressor p53, an important step in the development of cervical cancer (Scheffner et al., 1993).
Additionally, E6AP is associated with a variety of neurological disorders, including Angelman syndrome (AS), which results from loss or reduced expression of the maternally inherited UBE3A allele. In contrast, increased UBE3A expression has been associated with autism spectrum disorder (ASD).