Signal peptide
Encyclopedia
A signal peptide is a short (3-60 amino acid
s long) peptide
chain that directs the transport of a protein
.
Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals.
There is some confusion relating to the precise meaning of the term 'signal peptide'. Some sources refer to signal peptides as only the pre-sequence that targets the propeptide to the endoplasmic reticulum
and through the secretory pathway. Used in this system it does not refer to 'transit peptides'. A 'transit peptide' used in this system refers to the part of the pre-sequence that targets the protein to other organelles, such as mitochondria, chloroplast
s and apicoplast
s.
The amino acid sequences of signal peptides direct proteins (which are synthesized in the cytosol
) to certain organelle
s such as the nucleus
, mitochondrial matrix
, endoplasmic reticulum
, chloroplast
, apoplast
and peroxisome
. Some signal peptides are cleaved from the protein by signal peptidase after the proteins are transported.
have a sequence consisting of 5-10 hydrophobic amino acids on the N-terminus
.
The protein is guided to the ER by a signal-recognition particle (SRP), which moves between the ER and the cytoplasm. It binds to the signal peptide. The SRP binds to the signal peptide as soon as it is synthesized and extruded from the ribosome. This causes a pause in protein synthesis, most probably allowing the ribosome-SRP complex time to bind to the SRP receptor on the target ER membrane. The SRP is thought to be a regulatory GTP protein. Conformational changes may therefore lead to the SRP release. The protein may then be threaded through the ER membrane by a translocator pore.
Most of these proteins are transported from the endoplasmic reticulum to the Golgi apparatus
. If these proteins have a particular 4-amino-acid retention sequence, KDEL (lys-asp-glu-leu), on the C-terminus
, they are retained in the endoplasmic reticulum or are routed back to the ER (in instances where they escape) via interaction with the KDEL receptor in the Golgi apparatus. Many records now state that c-terminal KDEL in mammals, HDEL variants in yeast are conserved to be the re-router signals rather than ER retention signals.
(NLS) is a signal peptide directing to the nucleus and is often a unit consisting of five basic, positively-charged amino acids. The NLS normally is located anywhere on the peptide chain.
within the nucleus can be targeted with a sequence called a nucleolar localization signal (abbreviated NoLS or NOS).
has a sequence consisting of an alternating pattern (amphipathic helix)with a few hydrophobic amino acids and a few positively charged amino acids at the N terminus. It is usually called the mitochondrial targeting signal (MTS).
, which are called peroxisomal targeting signal
s (PTS). One is PTS1, which is made of three amino acids on the C-terminus. The other is PTS2, which is made of a 9-amino-acid sequence often present on the N-terminus of the protein.
(NLS) -Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val-
Transport to the endoplasmic reticulum
H2N-Met-Met-Ser-Phe-Val-Ser-Leu-
Leu-Leu-Val-Gly-Ile-Leu-Phe-
Trp-Ala-Thr-Glu-Ala-Glu-Gln-
Leu-Thr-Lys-Cys-Glu-Val-Phe-
Gln-
Retention to the endoplasmic reticulum
-Lys-Asp-Glu-Leu-COOH
Transport to the mitochondrial matrix
H2N-Met-Leu-Ser-Leu-Arg-Gln-Ser-
Ile-Arg-Phe-Phe-Lys-Pro-Ala-
Thr-Arg-Thr-Leu-Cys-Ser-Ser-
Arg-Tyr-Leu-Leu-
Transport to the peroxisome
(PTS1) -Ser-Lys-Leu-COOH
Transport to the peroxisome
(PTS2) H2N-----Arg-Leu-X5-His-Leu-
H2N is the N-terminus of a protein. COOH is the C-Terminus of a protein.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s long) peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
chain that directs the transport of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
.
Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals.
There is some confusion relating to the precise meaning of the term 'signal peptide'. Some sources refer to signal peptides as only the pre-sequence that targets the propeptide to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
and through the secretory pathway. Used in this system it does not refer to 'transit peptides'. A 'transit peptide' used in this system refers to the part of the pre-sequence that targets the protein to other organelles, such as mitochondria, chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...
s and apicoplast
Apicoplast
An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including malaria parasites such as Plasmodium falciparum, but not in others such as Cryptosporidium. It originated from an algae through secondary endosymbiosis...
s.
The amino acid sequences of signal peptides direct proteins (which are synthesized in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
) to certain organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s such as the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, mitochondrial matrix
Mitochondrial matrix
In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...
, endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...
, apoplast
Apoplast
Within a plant, the apoplast is the free diffusional space outside the plasma membrane. It is interrupted by the Casparian strip in roots, air spaces between plant cells and the cuticula of the plant....
and peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
. Some signal peptides are cleaved from the protein by signal peptidase after the proteins are transported.
Endoplasmic reticulum
Almost all proteins that are transported to the endoplasmic reticulumEndoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
have a sequence consisting of 5-10 hydrophobic amino acids on the N-terminus
N-terminal end
The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group . The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus...
.
The protein is guided to the ER by a signal-recognition particle (SRP), which moves between the ER and the cytoplasm. It binds to the signal peptide. The SRP binds to the signal peptide as soon as it is synthesized and extruded from the ribosome. This causes a pause in protein synthesis, most probably allowing the ribosome-SRP complex time to bind to the SRP receptor on the target ER membrane. The SRP is thought to be a regulatory GTP protein. Conformational changes may therefore lead to the SRP release. The protein may then be threaded through the ER membrane by a translocator pore.
Most of these proteins are transported from the endoplasmic reticulum to the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
. If these proteins have a particular 4-amino-acid retention sequence, KDEL (lys-asp-glu-leu), on the C-terminus
C-terminal end
The C-terminus is the end of an amino acid chain , terminated by a free carboxyl group . When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus...
, they are retained in the endoplasmic reticulum or are routed back to the ER (in instances where they escape) via interaction with the KDEL receptor in the Golgi apparatus. Many records now state that c-terminal KDEL in mammals, HDEL variants in yeast are conserved to be the re-router signals rather than ER retention signals.
Nucleus
A nuclear localization signalNuclear localization signal
A nuclear localization signal or sequence is an amino acid sequence which 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different...
(NLS) is a signal peptide directing to the nucleus and is often a unit consisting of five basic, positively-charged amino acids. The NLS normally is located anywhere on the peptide chain.
Nucleolus
The nucleolusNucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
within the nucleus can be targeted with a sequence called a nucleolar localization signal (abbreviated NoLS or NOS).
Mitochondrial matrix
The signal peptide that directs to the mitochondrial matrixMatrix (biology)
In biology, matrix is the material between animal or plant cells, in which more specialized structures are embedded, and a specific part of the mitochondrion that is the site of oxidation of organic molecules. The internal structure of connective tissues is an extracellular matrix...
has a sequence consisting of an alternating pattern (amphipathic helix)with a few hydrophobic amino acids and a few positively charged amino acids at the N terminus. It is usually called the mitochondrial targeting signal (MTS).
Peroxisome
There are two types of signal peptides directing to peroxisomePeroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
, which are called peroxisomal targeting signal
Peroxisomal targeting signal
A peroxisomal targeting signal is a region of the peroxisomal protein that receptors recognize and bind to.- Overview:All peroxisomal proteins are synthesized in the cytoplasm and must be directed to the peroxisome. The first step in this process is the binding of the protein to a receptor. The...
s (PTS). One is PTS1, which is made of three amino acids on the C-terminus. The other is PTS2, which is made of a 9-amino-acid sequence often present on the N-terminus of the protein.
Types
Following is a list of types of signal peptides:- N-terminus signal peptides often target the mitochondrial matrixMitochondrial matrixIn the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...
, endoplasmic reticulumEndoplasmic reticulumThe endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
and peroxisomePeroxisomePeroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
. - C-terminus signal peptides often target the peroxisomePeroxisomePeroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
.
Examples of signal peptides
Transport to the nucleusCell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
(NLS) -Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val-
Transport to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
H2N-Met-Met-Ser-Phe-Val-Ser-Leu-
Leu-Leu-Val-Gly-Ile-Leu-Phe-
Trp-Ala-Thr-Glu-Ala-Glu-Gln-
Leu-Thr-Lys-Cys-Glu-Val-Phe-
Gln-
Retention to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
-Lys-Asp-Glu-Leu-COOH
Transport to the mitochondrial matrix
Mitochondrial matrix
In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...
H2N-Met-Leu-Ser-Leu-Arg-Gln-Ser-
Ile-Arg-Phe-Phe-Lys-Pro-Ala-
Thr-Arg-Thr-Leu-Cys-Ser-Ser-
Arg-Tyr-Leu-Leu-
Transport to the peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
(PTS1) -Ser-Lys-Leu-COOH
Transport to the peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
(PTS2) H2N-----Arg-Leu-X5-His-Leu-
H2N is the N-terminus of a protein. COOH is the C-Terminus of a protein.
External links
- SPdb (Signal Peptide DataBase)
- SignalP — predicts the presence and location of signal peptide cleavage sites in amino acid sequences from different organisms.