C-terminus

<h2 id="chemistry">Chemistry</h2>
<p>Each amino acid has a carboxyl group and an <a href="/facts/Amine/JvfYJfP6">amine</a> group. Amino acids link to one another to form a chain by a <a href="/facts/Dehydration_reaction/dTAxlyRX">dehydration reaction</a> 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 <a href="/facts/N-terminal_end/yKYpuaBJ">N-terminus</a>. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus.<a class="footnote-ref" id="fnref:1" href="#fn:1"><sup>1</sup></a>
</p>
<h2 id="function">Function</h2>
<h3>C-terminal retention signals</h3>
<p>While the <a href="/facts/N-terminus/yKYpuaBJ">N-terminus</a> of a protein often contains <a href="/facts/Protein_targeting/R3B37xMM">targeting signals</a>, the C-terminus can contain retention signals for protein sorting. The most common <a href="/facts/ER_retention/L8XPRMjt">ER retention</a> signal is the amino acid sequence <a href="/facts/KDEL_(amino_acid_sequence)/CNKu7Pxc">-KDEL</a> (<a href="/facts/Lysine/CEetgA9L">Lys</a>-<a href="/facts/Aspartic_acid/9DFSFPa1">Asp</a>-<a href="/facts/Glutamic_acid/7oXbNcvu">Glu</a>-<a href="/facts/Leucine/X7YrkvA5">Leu</a>) or <a href="/facts/HDEL_(amino_acid_sequence)/YPuzCVJ1">-HDEL</a> (<a href="/facts/Histidine/le7781NF">His</a>-Asp-Glu-Leu) at the C-terminus.  This keeps the protein in the <a href="/facts/Endoplasmic_reticulum/DVbLA7GE">endoplasmic reticulum</a> and prevents it from entering the <a href="/facts/Secretory_pathway/VHk9eLAV">secretory pathway</a>.
</p>
<h3>Peroxisomal targeting signal</h3>
<p class="note">See also: <a href="/facts/Protein_targeting/R3B37xMM">Protein targeting to peroxisomes</a></p>
<p>The sequence -SKL (Ser-Lys-Leu) or similar near C-terminus serves as <a href="/facts/Peroxisomal_targeting_signal/zUN74gqe">peroxisomal targeting signal</a> 1, directing the protein into <a href="/facts/Peroxisome/sEW1RBmb">peroxisome</a>.
</p>
<h3>C-terminal modifications</h3>
<p>The C-terminus of proteins can be modified <a href="/facts/Posttranslational_modification/KMUayTIc">posttranslationally</a>, most commonly by the addition of a <a href="/facts/Lipid/TdQR87HX">lipid</a> anchor to the C-terminus that allows the protein to be inserted into a membrane without having a <a href="/facts/Transmembrane_domain/D1j0PwSR">transmembrane domain</a>.
</p>
<h4>Prenylation</h4>
<p class="note">Main article: <a href="/facts/Prenylation/M8owTu4H">Prenylation</a></p>
<p>One form of C-terminal modification is <a href="/facts/Prenylation/M8owTu4H">prenylation</a>. During prenylation, a <a href="/facts/Farnesyl_pyrophosphate/Ar8Mex9S">farnesyl</a>- or <a href="/facts/Geranylgeranyl_pyrophosphate/ShLNHtbI">geranylgeranyl</a>-isoprenoid membrane anchor is added to a <a href="/facts/Cysteine/kbqvUm6d">cysteine</a> residue near the C-terminus. Small, membrane-bound <a href="/facts/G_protein/HKkcfgGP">G proteins</a> are often modified this way.
</p>
<h4>GPI anchors</h4>
<p class="note">Main article: <a href="/facts/Glycosylphosphatidylinositol/dKsjvUTx">Glycosylphosphatidylinositol</a></p>
<p>Another form of C-terminal modification is the addition of a phosphoglycan, <a href="/facts/Glycosylphosphatidylinositol/dKsjvUTx">glycosylphosphatidylinositol</a> (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 <a href="/facts/Prion/UJfG9EfS">prion</a> protein.
</p>
<h4>Methylation</h4>
<p class="note">See also: <a href="/facts/Methylation/EvDMWVW5">Methylation</a> and <a href="/facts/(Phosphatase_2A_protein)-leucine-carboxy_methyltransferase/WhqgTtcE">(Phosphatase 2A protein)-leucine-carboxy methyltransferase</a></p>
<p>C-terminal <a href="/facts/Leucine/X7YrkvA5">leucine</a> is methylated at carboxyl group by enzyme <a href="/facts/Leucine_carboxyl_methyltransferase_1/dx6fITpN">leucine carboxyl methyltransferase 1</a> in vertebrates, forming <a href="/facts/Methyl_ester/FoUAIIw4">methyl ester</a>.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a>
</p>
<h3>C-terminal domain</h3>

<p>The C-terminal domain of some proteins has specialized functions. In humans, the CTD of <a href="/facts/RNA_polymerase_II/MK2kgybw">RNA polymerase II</a> typically consists of up to 52 <a href="/facts/Repeated_sequence_(DNA)/hPosWry7">repeats</a> of the sequence <a href="/facts/Tyrosine/RJhEgE4C">Tyr</a>-Ser-<a href="/facts/Proline/x1ABSW5A">Pro</a>-<a href="/facts/Threonine/7zffFQ6W">Thr</a>-Ser-Pro-Ser.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> 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 <a href="/facts/DNA_transcription/bDgp9HDN">initiation</a> of DNA transcription, the <a href="/facts/Capping_enzyme/P5ol1yP4">capping</a> of the <a href="/facts/Messenger_RNA/oUL6qxQn">RNA transcript</a>, and attachment to the <a href="/facts/Spliceosome/H3nnb6rd">spliceosome</a> for <a href="/facts/RNA_splicing/a2QEvCRI">RNA splicing</a>.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a>
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<h2 id="see-also">See also</h2>
<ul><li><a href="/facts/N-terminus/yKYpuaBJ">N-terminus</a></li>
<li><a href="/facts/TopFIND/k6r1qG4m">TopFIND</a>, a scientific database covering <a href="/facts/Protease/G1ASdVat">proteases</a>, their cleavage site specificity, substrates, inhibitors and protein termini originating from their activity</li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1"><p>Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter (2002). "From RNA to Protein". Molecular Biology of the Cell. 4th edition. Garland Science. <a href="https://www.ncbi.nlm.nih.gov/books/NBK26829/#:~:text=Consequently%2C%20a%20protein%20is%20synthesized,a%20peptidyl%2DtRNA%20molecule)." target="_blank">https://www.ncbi.nlm.nih.gov/books/NBK26829/#:~:text=Consequently%2C%20a%20protein%20is%20synthesized,a%20peptidyl%2DtRNA%20molecule).</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li>
<li id="fn:2"><p>"RHEA:48544". Swiss Institute of Bioinformatics. <a href="https://www.rhea-db.org/rhea/48544" target="_blank">https://www.rhea-db.org/rhea/48544</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li>
<li id="fn:3"><p>Meinhart A, Cramer P (July 2004). "Recognition of RNA polymerase II carboxy-terminal domain by 3'-RNA-processing factors". Nature. 430 (6996): 223–6. Bibcode:2004Natur.430..223M. doi:10.1038/nature02679. hdl:11858/00-001M-0000-0015-8512-8. PMID 15241417. S2CID 4418258. <a href="https://resolver.sub.uni-goettingen.de/purl?gro-2/1538" target="_blank">https://resolver.sub.uni-goettingen.de/purl?gro-2/1538</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li>
<li id="fn:4"><p>Brickey WJ, Greenleaf AL (June 1995). "Functional studies of the carboxy-terminal repeat domain of Drosophila RNA polymerase II in vivo". Genetics. 140 (2): 599–613. doi:10.1093/genetics/140.2.599. PMC 1206638. PMID 7498740. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1206638" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1206638</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li>
</ol>

C-terminus open-in-new

C-terminus