N-terminal end
The N-terminus refers to the start of a 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...

 or polypeptide terminated by an amino acid
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...

 with a free amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

 group (-NH2). The convention for writing peptide sequences is to put the N-terminus on the left and write the sequence from N- to C-terminus. When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus.


Each amino acid has a carboxyl group and an amine group, and amino acids link to one another to form a chain by a dehydration reaction
Dehydration reaction
In chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical reaction that involves the loss of water from the reacting molecule. Dehydration reactions are a subset of elimination reactions...

 by joining the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an amine group, the N-terminus.

When the protein is translated from messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

, it is created from N-terminus to C-terminus. The amino end of an amino acid (on a charged tRNA
Transfer RNA
Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...

) during the elongation stage of translation, attaches to the carboxyl end of the growing or nascent chain. Since the start codon
Start codon
The start codon is generally defined as the point, sequence, at which a ribosome begins to translate a sequence of RNA into amino acids.When an RNA transcript is "read" from the 5' carbon to the 3' carbon by the ribosome the start codon is the first codon on which the tRNA bound to Met,...

 of the genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....

 codes for the amino acid methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...

, most protein sequences start with a methionine (more specifically: the modified version N-formylmethionine
N-Formylmethionine is a proteinogenic amino acid found in Bacteria and related Prokaryotic organelles. It is a derivative of the amino acid methionine in which a formyl group has been added to the amino group...

, fMet). However, some proteins are modified posttranslationally
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....

, for example by cleavage from a protein precursor
Protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein that can be turned into an active form by posttranslational modification. The name of the precursor for a protein is often prefixed by pro...

, and therefore may have different amino acids at their N-terminus.

N-terminal targeting signals

The N-terminus is the first part of the protein that exits the ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 during protein biosynthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

. It often contains signal peptide
Signal peptide
A signal peptide is a short peptide chain that directs the transport of a protein.Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals....

 sequences, "intracellular postal code
Postal code
A postal code is a series of letters and/or digits appended to a postal address for the purpose of sorting mail. Once postal codes were introduced, other applications became possible.In February 2005, 117 of the 190 member countries of the Universal Postal Union had postal code systems...

s" that direct delivery of the protein to the proper 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....

. The signal peptide is typically removed at the destination by a signal peptidase. The N-terminal amino acid of a protein is an important determinant of its half-life (likelihood of being degraded). This is called the N-end rule
N-end rule
The N-end rule is a rule related to ubiquitination, discovered by Alexander Varshavsky in 1986. The rule, which states that the nature of the N-terminal amino acids of a protein is an important factor that governs its half-life , is applicable to both eukaryotic and prokaryotic organisms, but with...

  • Signal peptide

The N-terminal signal peptide is recognized by the signal recognition particle
Signal recognition particle
The signal recognition particle is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes....

 (SRP) and results in the targeting of the protein to the secretory pathway
Secretory pathway
The secretory pathway is a series of steps a cell uses to move proteins out of the cell; a process known as secretion. The path of a protein destined for secretion has its origins in the rough endoplasmic reticulum, a membrane-bound compartment in the cell...

. In eukaryotic cells
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

, these proteins are synthesized at the rough 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...

. In prokaryotic cells
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...

, the proteins are exported across the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

. In 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, signal peptides target proteins to the thylakoid
A thylakoid is a membrane-bound compartment inside chloroplasts and cyanobacteria. They are the site of the light-dependent reactions of photosynthesis. Thylakoids consist of a thylakoid membrane surrounding a thylakoid lumen. Chloroplast thylakoids frequently form stacks of disks referred to as...

  • Mitochondrial targeting peptide

The N-terminal mitochondrial targeting peptide (mtTP) allows for the protein to be imported into the mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...

  • Chloroplast targeting peptide

The N-terminal chloroplast targeting peptide (cpTP) allows for the protein to be imported into the 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...


N-terminal modifications

Some proteins are modified posttranslationally by the addition of membrane anchors that allow the protein to associate with membrane without having a transmembrane domain. The N-terminus (as well as the C-terminus) of a protein can be modified this way.
  • N-Myristoylation

The N-terminus can be modified by the addition of a myristoyl anchor. Proteins that are modified this way contain a consensus motif at their N-terminus as a modification signal.
  • N-Acylation

The N-terminus can also be modified by the addition of a fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...

 anchor to form N-acylated proteins. The most common form of such modification is the addition of a palmitoyl group.
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