The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

chain (

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

), terminated by a free carboxyl group (-COOH). When the protein is translated from

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

, it is created from

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus.

Chemistry

Each amino acid has a carboxyl group and an

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

group. Amino acids link to one another to form a chain by a

dehydration reaction In chemistry, a dehydration reaction is a chemical reaction that involves the loss of an H2O from the reacting molecule(s) or ion(s). This reaction results in the release of the H2O as water. When the reaction involves the coupling of two molecu ...

which joins 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 unbound amine group, the

. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus.

Function

C-terminal retention signals

While the

of a protein often contains targeting signals, the C-terminus can contain retention signals for protein sorting. The most common ER retention signal is the amino acid sequence -KDEL ( Lys- Asp- Glu- Leu) or -HDEL ( His-Asp-Glu-Leu) at the C-terminus. This keeps the protein in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

and prevents it from entering the

secretory pathway Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell (biology), cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. Th ...

Peroxisomal targeting signal

The sequence -SKL (Ser-Lys-Leu) or similar near C-terminus serves as peroxisomal targeting signal 1, directing the protein into

peroxisome A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen perox ...

C-terminal modifications

The C-terminus of proteins can be modified posttranslationally, most commonly by the addition of a

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

anchor to the C-terminus that allows the protein to be inserted into a membrane without having a transmembrane domain.

Prenylation

One form of C-terminal modification is prenylation. During prenylation, a farnesyl- or geranylgeranyl-isoprenoid membrane anchor is added to a

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residue near the C-terminus. Small, membrane-bound

G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...

s are often modified this way.

GPI anchors

Another form of C-terminal modification is the addition of a phosphoglycan, glycosylphosphatidylinositol (GPI), as a membrane anchor. The GPI anchor is attached to the C-terminus after proteolytic cleavage of a C-terminal propeptide. The most prominent example for this type of modification is the

prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...

protein.

Methylation

C-terminal

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-Car ...

is methylated at carboxyl group by enzyme leucine carboxyl methyltransferase 1 in vertebrates, forming methyl ester.

C-terminal domain

The C-terminal domain of some proteins has specialized functions. In humans, the CTD of

RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...

typically consists of up to 52 repeats of the sequence Tyr-Ser- Pro- Thr-Ser-Pro-Ser. This allows other proteins to bind to the C-terminal domain of RNA polymerase in order to activate polymerase activity. These domains are then involved in the

initiation Initiation is a rite of passage marking entrance or acceptance into a group or society. It could also be a formal admission to adulthood in a community or one of its formal components. In an extended sense, it can also signify a transformatio ...

of DNA transcription, the capping of the RNA transcript, and attachment to the spliceosome for

RNA splicing RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcription (biology), transcript is transformed into a mature messenger RNA (Messenger RNA, mRNA). It works by removing all the introns (non-cod ...

References

{{DEFAULTSORT:C-Terminus Post-translational modification Protein structure