AMFR - E3 ubiquitin-protein ligase AMFR | Elisa - Clia - Antibody - Protein

Background:

E3 ubiquitin-protein ligase AMFR, also known as autocrine motility factor receptor (AMFR), is an enzyme that plays a crucial role in the ubiquitin-proteasome system (UPS), which is responsible for the targeted degradation of proteins within cells. AMFR functions as an E3 ubiquitin ligase, which means it catalyzes the transfer of ubiquitin molecules from E2 ubiquitin-conjugating enzymes to target proteins, marking them for degradation by the proteasome. This process, known as ubiquitination, is essential for regulating various cellular processes, including protein turnover, signal transduction, and the maintenance of protein homeostasis. AMFR has been implicated in other cellular functions: Regulation of protein trafficking: AMFR is involved in the quality control of membrane proteins, particularly those destined for degradation in the endoplasmic reticulum-associated degradation (ERAD) pathway. It helps target misfolded or unassembled membrane proteins for ubiquitination and subsequent degradation by the proteasome. Regulation of cellular signaling: AMFR has been shown to interact with and regulate various signaling molecules and pathways, including the epidermal growth factor receptor (EGFR) signaling pathway. It can modulate the activity and stability of proteins involved in cell proliferation, survival, and migration.Dysregulation of AMFR expression or activity has been implicated in various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases. In cancer, for example, AMFR overexpression has been associated with tumor progression, metastasis, and resistance to chemotherapy.

Protein Structure:

• Molecular Weight: Approximately 78 kDa.
• Domains: AMFR contains a RING finger domain essential for its E3 ubiquitin ligase activity, a transmembrane domain, and a cytoplasmic tail that interacts with various substrates and cofactors.
• Localization: AMFR is localized mainly to the endoplasmic reticulum (ER) membrane but is also found on the cell surface.

Classification and Subtypes:

• Family: AMFR belongs to the RING finger E3 ubiquitin ligases, which are characterized by their ability to facilitate the transfer of ubiquitin from E2 ubiquitin-conjugating enzymes to target substrates.
• Subtypes: There are no distinct subtypes of AMFR, but it interacts with various proteins and cofactors that modulate its function.

Function and Biological Significance:

• Ubiquitination: AMFR functions as an E3 ubiquitin ligase, tagging misfolded or damaged proteins for degradation by the proteasome, a key process in maintaining cellular homeostasis.
• ERAD Pathway: AMFR is crucial in the ER-associated degradation pathway, identifying and marking misfolded proteins in the ER for proteasomal degradation.
• Cell Motility: As a receptor for AMF, AMFR influences cell migration and motility, which is important in processes such as wound healing and cancer metastasis.
• Signal Transduction: AMFR is involved in various signaling pathways that regulate cell growth, apoptosis, and immune responses.

Interactions:

• Ubiquitin-Proteasome System Components: AMFR interacts with several components of the ubiquitin-proteasome system, including E2 ubiquitin-conjugating enzymes.
• Co-factors and Substrates: AMFR binds to various cofactors and substrates that modulate its E3 ligase activity and its role in ERAD.
• Cell Surface Receptors: AMFR can interact with other cell surface receptors and signaling molecules, influencing cellular signaling and motility.

Clinical Issues:

• Cancer: AMFR is implicated in cancer progression and metastasis due to its role in promoting cell motility and invasion. Overexpression of AMFR is often associated with poor prognosis in various cancers.
• Neurodegenerative Diseases: Dysfunction in the ERAD pathway, involving AMFR, has been linked to neurodegenerative disorders, highlighting its importance in protein quality control.
• Inflammatory Diseases: AMFR has a role in regulating immune responses, and dysregulation of its activity may contribute to inflammatory conditions.

Summary:

AMFR (E3 ubiquitin-protein ligase AMFR) is a critical component of the ubiquitin-proteasome system, functioning primarily as an E3 ubiquitin ligase. It plays a vital role in the ER-associated degradation pathway, helping maintain cellular protein homeostasis by targeting misfolded proteins for degradation. AMFR is also involved in cell motility and signal transduction, influencing processes such as cancer metastasis and immune responses. Given its involvement in key cellular functions and disease processes, AMFR is a significant focus of research, particularly in cancer and neurodegenerative diseases.