Protein subcellular localization prediction (or just protein localization prediction) involves the prediction of where a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

resides in a cell, its

subcellular localization The cells of eukaryotic organisms are elaborately subdivided into functionally-distinct membrane-bound compartments. Some major constituents of eukaryotic cells are: extracellular space, plasma membrane, cytoplasm, nucleus, mitochondria, Golgi ...

. In general, prediction tools take as input information about a protein, such as a protein sequence of

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

s, and produce a predicted location within the cell as output, such as the nucleus, Endoplasmic reticulum, Golgi apparatus, extracellular space, or other

organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...

s. The aim is to build tools that can accurately predict the outcome of

protein targeting :''This article deals with protein targeting in eukaryotes unless specified otherwise.'' Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the ce ...

in cells. Prediction of protein subcellular localization is an important component of bioinformatics based prediction of

protein function Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respond ...

and genome annotation, and it can aid the identification of drug targets.

Background

Experimentally determining the

of a

can be a laborious and time consuming task. Immunolabeling or tagging (such as with a green fluorescent protein) to view localization using fluorescence microscope are often used. A high throughput alternative is to use prediction. Through the development of new approaches in computer science, coupled with an increased dataset of proteins of known localization, computational tools can now provide fast and accurate localization predictions for many organisms. This has resulted in subcellular localization prediction becoming one of the challenges being successfully aided by bioinformatics, and machine learning. Many prediction methods now exceed the accuracy of some high-throughput laboratory methods for the identification of protein subcellular localization. Particularly, some predictors have been developed that can be used to deal with proteins that may simultaneously exist, or move between, two or more different subcellular locations. Experimental validation is typically required to confirm the predicted localizations.

Tools

In 1999

PSORT PSORT is a bioinformatics tool used for the prediction of protein localisation sites in cells. It receives the information of an amino acid sequence and its taxon of origin (e.g. Gram-negative bacteria) as inputs. Then it analyses the input seque ...

was the first published program to predict subcellular localization. Subsequent tools and websites have been released using techniques such as artificial neural networks,

support vector machine In machine learning, support vector machines (SVMs, also support vector networks) are supervised learning models with associated learning algorithms that analyze data for classification and regression analysis. Developed at AT&T Bell Laboratorie ...

and

protein motif In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have t ...

s. Predictors can be specialized for proteins in different organisms. Some are specialized for eukaryotic proteins, some for human proteins, and some for plant proteins. Methods for the prediction of bacterial localization predictors, and their accuracy, have been reviewed. In 2021, SCLpred-MEM, a membrane protein prediction tool powered by artificial neural networks was published. SCLpred-EMS is another tool powered by Artificial neural networks that classify proteins into endomembrane system and secretory pathway (EMS) versus all others. Similarly, Light-Attention uses machine learning methods to predict ten different common subcellular locations. The development of protein subcellular location prediction has been summarized in two comprehensive review articles. Recent tools and an experience report can be found in a recent paper b
Meinken and Min (2012)

Application

Knowledge of the subcellular localization of a protein can significantly improve target identification during the drug discovery process. For example, secreted proteins and

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

proteins are easily accessible by drug molecules due to their localization in the extracellular space or on the cell surface. Bacterial cell surface and secreted proteins are also of interest for their potential as vaccine candidates or as diagnostic targets. Aberrant subcellular localization of proteins has been observed in the cells of several diseases, such as

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

and Alzheimer's disease. Secreted proteins from some archaea that can survive in unusual environments have industrially important applications. By using prediction a high number of proteins can be assessed in order to find candidates that are trafficked to the desired location.

Databases

The results of subcellular localization prediction can be stored in databases. Examples include the multi-species databas
Compartments
FunSecKB2, a fungal database; PlantSecKB, a plant database; MetazSecKB, an animal and human database; and ProtSecKB, a protist database.

Background

Tools

Application

Databases

References

Further reading