Interactive
The POMC cleavage tree
One inert precursor is cut, step by step, into the whole melanocortin family. The twist is that where the cutting happens decides what gets made. Switch the tissue below and watch the tree change: the anterior pituitary stops at ACTH, while the brain and skin carry a second enzyme that unlocks α-MSH, β-endorphin, and the rest.
Where is POMC being processed?
- Melanocortin
- Processing intermediate
- Opioid peptide
- Other fragment
- PC1/3 first cut
- PC2 second cut
Select any peptide in the tree to see what it is, which enzyme cuts it out, and what it does.
One gene, two scissors
POMC is a prohormone: a long, inactive chain that only becomes useful once it is cut. The cutting is done by prohormone convertases, enzymes that recognise pairs of basic amino acids and snip the chain there. Two of them do almost all the branching. PC1/3 makes the first cuts and is present in every POMC-expressing cell, releasing the N-terminal fragment, the joining peptide, ACTH, and β-lipotropin. PC2 makes a second round of cuts — but only in tissues that carry it.
That is the whole trick of the system’s economy. In the anterior pituitary, which lacks PC2, processing stops at ACTH: the gland’s job is the cortisol stress axis. In the hypothalamus, the skin, and the intermediate lobe of the pituitary, PC2 keeps going — cutting ACTH into α-MSH, β-lipotropin into β-endorphin, and liberating β- and γ-MSH. Same precursor, same first cuts, a different set of final messengers, decided entirely by which scissors the cell owns.
The finishing touches
A few more enzymes tidy up the ends after the convertases cut. Carboxypeptidase E trims the leftover basic residues from each new C-terminus; the amidating enzyme PAM caps many of the peptides with an amide; and an N-acetyltransferase acetylates α-MSH at its front end, which stabilises it and sharpens its activity. These steps are why the mature α-MSH is written as acetyl-ACTH(1–13)-amide rather than a bare fragment — but they trim and cap rather than branch, so they sit off the tree above.
What is not on the tree
Two important players are missing by design. The system’s natural brakes — agouti signalling protein and AgRP — are antagonists at the melanocortin receptors, but they are made from their own separate genes, not cut from POMC. And β-endorphin, though it rides out of the same precursor, is an opioid, not a melanocortin: it is the clearest sign of how much functional range one gene can hold. For the bigger picture of how these products act once released, see the melanocortin system and the five receptors that read them.
Common questions
What is the POMC cleavage tree?
It is the branching set of peptides produced when the precursor protein pro-opiomelanocortin (POMC) is cut by enzymes. POMC is biologically inert until prohormone convertases snip it at pairs of basic amino acids, releasing — step by step — ACTH, the melanocyte-stimulating hormones (α-, β- and γ-MSH), and β-endorphin.
Why does the same POMC gene make ACTH in the pituitary but α-MSH in the brain and skin?
Because the tissues carry different enzymes. The first cuts are made by prohormone convertase PC1/3, which is present everywhere POMC is made, and they stop at ACTH and β-lipotropin. The second round of cuts needs PC2, which is present in the hypothalamus, skin and intermediate lobe of the pituitary but not in anterior-pituitary corticotrophs. Only where PC2 is present does ACTH get cut further into α-MSH.
Which POMC products are melanocortins and which are not?
The melanocortins — the peptides that act on the MC1R–MC5R receptors through a shared His-Phe-Arg-Trp core — are α-, β- and γ-MSH and ACTH. The same precursor also releases β-endorphin, an opioid peptide that acts on the opioid receptors, plus processing fragments such as the joining peptide and CLIP that have no melanocortin activity.
Are agouti and AgRP part of the POMC tree?
No. Agouti signalling protein (ASIP) and agouti-related peptide (AgRP) are the system’s two natural brakes, but they are made from their own separate genes — they are not cut from POMC. They act as antagonists at the same receptors the POMC melanocortins switch on.
References
- 1.Harno E, Gali Ramamoorthy T, Coll AP, White A. POMC: The Physiological Power of Hormone Processing. Physiol Rev. 98(4):2381–2430. 2018. link ↗
- 2.Cawley NX, Li Z, Loh YP. Biosynthesis, trafficking, and secretion of POMC-derived peptides. Review (PMC4899099). 2016. link ↗
- 3.Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 27(7):736–49. 2006. link ↗