Proopiomelanocortin

Pro-opiomelanocortin (POMC) is a precursor is_associated_with::polypeptide with 241 is_associated_with::amino acid residues. POMC is synthesized from the 285-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-amino-acid-long is_associated_with::signal peptide sequence during translation.

Function
POMC is cleaved to give rise to multiple is_associated_with::peptide hormones. Each of these peptides is packaged in large dense-core vesicles that are released from the cells by is_associated_with::exocytosis in response to appropriate stimulation:


 * α-MSH produced by neurons in the is_associated_with::arcuate nucleus has important roles in the regulation of is_associated_with::appetite and sexual behavior, while α-MSH secreted from the intermediate lobe of the is_associated_with::pituitary regulates the production of is_associated_with::melanin.
 * is_associated_with::ACTH is a is_associated_with::peptide hormone that regulates the secretion of is_associated_with::glucocorticoids from the is_associated_with::adrenal cortex.
 * β-Endorphin and [Met]enkephalin are endogenous is_associated_with::opioid peptides with widespread actions in the brain.

Synthesis
The POMC gene is located on chromosome 2p23.3. The POMC gene is expressed in both the anterior and intermediate lobes of the pituitary gland. This gene encodes a 285-amino acid polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by is_associated_with::subtilisin-like enzymes known as prohormone convertases. The encoded protein is synthesized mainly in corticotroph cells of the anterior is_associated_with::pituitary, where four cleavage sites are used; adrenocorticotrophin (ACTH), essential for normal is_associated_with::steroidogenesis and the maintenance of normal adrenal weight, and β-lipotropin are the major end-products. However, there are at least eight potential cleavage sites within the polypeptide precursor and, depending on tissue type and the available convertases, processing may yield as many as ten biologically active peptides involved in diverse cellular functions. Cleavage sites consist of the sequences Arg-Lys, Lys-Arg, or Lys-Lys. Enzymes responsible for processing of POMC peptides include is_associated_with::prohormone convertase 1 (PC1), is_associated_with::prohormone convertase 2 (PC2), is_associated_with::carboxypeptidase E (CPE), peptidyl α-amidating monooxygenase (PAM), N-acetyltransferase (N-AT), and prolylcarboxypeptidase (PRCP).

The processing of POMC involves glycosylations, acetylations, and extensive proteolytic cleavage at sites shown to contain regions of basic protein sequences. However, the proteases that recognize these cleavage sites are tissue-specific. In some tissues, including the is_associated_with::hypothalamus, is_associated_with::placenta, and is_associated_with::epithelium, all cleavage sites may be used, giving rise to peptides with roles in pain and energy is_associated_with::homeostasis, is_associated_with::melanocyte stimulation, and immune modulation. These include several distinct is_associated_with::melanotropins, is_associated_with::lipotropins, and is_associated_with::endorphins that are contained within the adrenocorticotrophin and β-lipotropin peptides.

It is synthesized by:


 * is_associated_with::Corticotrope cells of the is_associated_with::anterior pituitary gland
 * is_associated_with::Melanotrope cells of the is_associated_with::intermediate lobe of the is_associated_with::pituitary gland
 * 3,148±62 Neurons in the is_associated_with::arcuate nucleus of the is_associated_with::hypothalamus
 * Smaller populations of neurons in the is_associated_with::dorsomedial hypothalamus and is_associated_with::brainstem
 * is_associated_with::Melanocytes in the skin

Derivatives
The large molecule of POMC is the source of several important biologically active substances. POMC can be cleaved enzymatically into the following is_associated_with::peptides:


 * N-Terminal Peptide of Proopiomelanocortin (NPP, or pro-γ-MSH)
 * γ-Melanotropin (γ-MSH)
 * is_associated_with::Corticotropin (Adrenocorticotropic Hormone, or ACTH)
 * α-Melanotropin (α-Melanocyte-Stimulating Hormone, or α-MSH)
 * Corticotropin-like Intermediate Peptide (CLIP)
 * β-Lipotropin (β-LPH)
 * Lipotropin Gamma (γ-LPH)
 * β-Melanotropin (β-MSH)
 * β-Endorphin
 * [Met]Enkephalin

Although the N-terminal 5 amino acids of is_associated_with::β-endorphin are identical to the sequence of [Met]enkephalin, it is not generally thought that β-endorphin is converted into [Met]enkephalin. Instead, [Met]enkephalin is produced from its own precursor, is_associated_with::proenkephalin A.

The production of β-MSH occurs in humans but not in mice or rats due to the absence of the enzymatic processing site in the rodent POMC.

Clinical significance
Mutations in this gene have been associated with early onset is_associated_with::obesity, is_associated_with::adrenal insufficiency, and is_associated_with::red hair is_associated_with::pigmentation. Alternatively spliced transcript variants encoding the same protein have been described.

Interactions
Proopiomelanocortin has been shown to interact with is_associated_with::melanocortin 4 receptor.