Functional Hotspots are small areas in the protein that carry a specific function - it can be a site that binds a cofactor or substrate, a site which is modified after translation is finished, for example, a lipid can be attached to this site or it can be phosphorylated.
Some sites can also be crucial for linking to other proteins - they act like a docking port.
Gene Inspector uses data provided by Uniprot to find variants in your genome that impact these hotspots. If genes with such variants are found, they are listed in the panel "Functional Hotspots":
Binding Site
A binding site is a specific spot on a protein where another molecule attaches. For example, a protein might have a binding site for a metal ion like calcium or for a drug molecule. These sites are like docking stations, allowing the protein to interact with other molecules and perform its function.
Example: The oxygen-binding site on hemoglobin allows it to carry oxygen in your blood.
Active Site
The active site is the region on an enzyme where the actual chemical reaction happens. It’s usually made up of a few special amino acids that help transform the molecule the enzyme is working on (called the substrate).
Example: In the enzyme lactase, the active site binds to lactose (milk sugar) and breaks it down into simpler sugars.
Modified Residue
A modified residue is an amino acid in a protein that has been chemically changed after the protein is made. These changes can affect how the protein works, where it goes in the cell, or how long it lasts.
Example: Phosphorylation is a common modification where a phosphate group is added to an amino acid, turning enzymes on or off in cell signaling pathways.
Cross-Link
A cross-link is a special connection between two parts of a protein or between two different proteins. This helps stabilize the protein’s structure or join proteins together for a specific function.
Example: In collagen (a protein in skin and bones), cross-links between protein chains make the structure strong and resilient.
Mutagenesis Site
A “mutagenesis site” refers to a specific amino acid residue or region in a protein sequence that has been experimentally altered through mutagenesis to study its effect on the protein’s structure, function, or biological properties.
This annotation is part of UniProt’s detailed sequence feature information and is typically found in the “Phenotypes and variants” or “Disease and variants” sections of a protein entry.
Experimental Alteration
The site has been intentionally mutated in laboratory experiments (e.g., by site-directed mutagenesis) to observe how changing that particular residue affects the protein.
Purpose
Mutagenesis site data help researchers understand the functional importance of specific amino acids, identify critical residues for activity, stability, or interactions, and interpret the functional consequences of naturally occurring or disease-associated variants.
Glycosylation Site
A glycosylation site is a position in a protein where a sugar molecule is attached. This sugar can help the protein fold properly, be recognized by other cells, or be protected from breakdown.
Example: Many antibodies have glycosylation sites that help them function correctly in the immune system.
Disulfide Bond
A disulfide bond is a strong link formed between two sulfur atoms from cysteine amino acids in a protein. These bonds help maintain the protein’s 3D shape, which is crucial for its function.
Example: Disulfide bonds in insulin help hold its two chains together, allowing it to work as a hormone.
Lipidation
Lipidation is the attachment of a fatty molecule (lipid) to a protein. This modification often helps the protein stick to cell membranes or move to specific parts of the cell.
Example: The protein Ras, important in cell growth, is lipidated so it can attach to the inside of the cell membrane and send signals.