TheC-terminus (also known as thecarboxyl-terminus,carboxy-terminus,C-terminal tail,carboxy tail,C-terminal end, orCOOH-terminus) is the end of anamino acid chain (protein orpolypeptide), terminated by a freecarboxyl group (-COOH). When the protein is translated from messenger RNA, it is created fromN-terminus 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.

Each amino acid has a carboxyl group and anamine group. Amino acids link to one another to form a chain by adehydration reaction 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, theN-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus.^[1]

While theN-terminus of a protein often containstargeting signals, the C-terminus can contain retention signals for protein sorting. The most commonER 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 theendoplasmic reticulum and prevents it from entering thesecretory pathway.

The sequence -SKL (Ser-Lys-Leu) or similar near C-terminus serves asperoxisomal targeting signal 1, directing the protein intoperoxisome.^{[citation needed]}

The C-terminus of proteins can be modifiedposttranslationally, most commonly by the addition of alipid anchor to the C-terminus that allows the protein to be inserted into a membrane without having atransmembrane domain.

One form of C-terminal modification isprenylation. During prenylation, afarnesyl- orgeranylgeranyl-isoprenoid membrane anchor is added to acysteine residue near the C-terminus. Small, membrane-boundG proteins are often modified this way.^{[citation needed]}

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 theprion protein.

C-terminalleucine is methylated at carboxyl group by enzymeleucine carboxyl methyltransferase 1 in vertebrates, formingmethyl ester.^[2]

The C-terminal domain of some proteins has specialized functions. In humans, the CTD ofRNA polymerase II typically consists of up to 52repeats of the sequenceTyr-Ser-Pro-Thr-Ser-Pro-Ser.^[3] 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 theinitiation of DNA transcription, thecapping of theRNA transcript, and attachment to thespliceosome forRNA splicing.^[4]

• N-terminus
• TopFIND, a scientific database coveringproteases, their cleavage site specificity, substrates, inhibitors and protein termini originating from their activity