ANPEP - alanyl aminopeptidase, membrane|Elisa - Clia - Antibody - Protein

Background:

ANPEP or Aminopeptidase N, also known as CD13 (Cluster of Differentiation 13). It is a cell surface metalloprotease enzyme that plays various roles in the body, particularly in the metabolism of peptides. ANPEP is a type II integral membrane glycoprotein, meaning it spans the cell membrane once.It belongs to the M1 family of zinc metallopeptidases, characterized by its zinc-dependent enzymatic activity. ANPEP catalyzes the removal of amino acids from the N-terminus of peptides and proteins. It acts on a wide range of substrates, including small peptides, proteins, and even some hormones. ANPEP is also involved in immune regulation, as it can cleave certain immune-modulating peptides. It plays a role in cell adhesion, migration, and signaling pathways. ANPEP can metabolize certain drugs, affecting their pharmacokinetics and bioavailability. ANPEP is found in the brush border membrane of the small intestine, where it participates in the digestion of dietary proteins. It is also present on the surface of various immune cells, such as monocytes, macrophages, and dendritic cells, where it helps regulate immune responses. ANPEP is often overexpressed in certain cancers, particularly in leukemia and some solid tumors. Its expression is associated with tumor progression and metastasis.

Protein Structure:

• Type II Transmembrane Protein: ANPEP is a single-pass transmembrane protein with a short N-terminal cytoplasmic domain, a transmembrane region, and a large extracellular C-terminal domain.
• Catalytic Domain: The extracellular portion contains the catalytic domain with a zinc-binding motif essential for its enzymatic activity.
• Glycosylation Sites: Multiple N-linked glycosylation sites contribute to the stability and function of the protein.

Classification and Subtypes:

ANPEP is a member of the M1 family of aminopeptidases, which are characterized by their ability to remove N-terminal amino acids from peptide substrates. There are no major subtypes of ANPEP, but its homologs and related enzymes in the M1 family include:

• Aminopeptidase A (ENPEP)
• Leucine Aminopeptidase (LAP3)
• Puromycin-sensitive Aminopeptidase (NPEPPS)

Function and Biological Significance:

• Peptide Digestion: ANPEP hydrolyzes N-terminal amino acids from peptides and proteins, playing a significant role in protein turnover and processing.
• Antigen Presentation: In immune cells, ANPEP contributes to the processing of antigenic peptides for presentation on MHC class I molecules.
• Cell Migration and Invasion: ANPEP is involved in processes like angiogenesis and tumor metastasis by modulating cell adhesion and migration.
• Hormone and Cytokine Regulation: ANPEP regulates the activity of various bioactive peptides, hormones, and cytokines by cleaving them, influencing immune responses and inflammation.

Interactions:

• Integrins: ANPEP interacts with integrins, affecting cell adhesion and migration, which is important in angiogenesis and metastasis.
• Cytokines and Chemokines: ANPEP can modulate the activity of cytokines and chemokines, influencing immune cell function and inflammatory responses.
• Other Proteases: ANPEP often works in concert with other proteases in protein degradation pathways.

Clinical Issues:

• Cancer: Overexpression of ANPEP has been observed in various cancers, including renal cell carcinoma, prostate cancer, and melanoma. It is associated with tumor progression, angiogenesis, and metastasis.
• Inflammatory Diseases: ANPEP is involved in the regulation of inflammatory responses and has been implicated in diseases such as rheumatoid arthritis and inflammatory bowel disease.
• Viral Infections: ANPEP serves as a receptor for certain coronaviruses, including the one responsible for porcine epidemic diarrhea virus (PEDV), highlighting its role in infectious diseases.

Summary:

Aminopeptidase N (ANPEP), also known as CD13, is a versatile enzyme involved in peptide digestion, immune response, cell migration, and angiogenesis. As a type II transmembrane protein, it has a catalytic domain essential for its proteolytic activity and multiple glycosylation sites for stability. ANPEP plays critical roles in various physiological and pathological processes, including cancer progression, inflammatory diseases, and viral infections. Understanding its functions and interactions opens potential avenues for therapeutic interventions targeting ANPEP in various diseases.