POMC
Identifiers
Aliases	POMC, ACTH, CLIP, LPH, MSH, NPP, POC, proopiomelanocortin, OBAIRH
External IDs	OMIM: 176830 MGI: 97742 HomoloGene: 723 GeneCards: POMC
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p23.3 Start 25,160,853 bp[1] End 25,168,903 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 A1.1|12 1.99 cM Start 3,954,951 bp[2] End 3,960,642 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • type 3 melanocortin receptor binding • hormone activity • type 1 melanocortin receptor binding • receptor binding • G-protein coupled receptor binding • type 4 melanocortin receptor binding • neuropeptide hormone activity Cellular component • cytoplasm • peroxisome • extracellular region • peroxisomal matrix • secretory granule lumen • extracellular space • secretory granule Biological process • glucose homeostasis • cellular pigmentation • cell-cell signaling • generation of precursor metabolites and energy • regulation of glycogen metabolic process • regulation of blood pressure • negative regulation of tumor necrosis factor production • regulation of appetite • signal transduction • positive regulation of transcription from RNA polymerase II promoter • neuropeptide signaling pathway • positive regulation of neutrophil mediated killing of fungus • regulation of corticosterone secretion • regulation of receptor activity • G-protein coupled receptor signaling pathway • cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5443	18976
Ensembl	ENSG00000115138	ENSMUSG00000020660
UniProt	P01189	P01193
RefSeq (mRNA)	NM_000939 NM_001035256 NM_001319204 NM_001319205	NM_008895 NM_001278581 NM_001278582 NM_001278583 NM_001278584
RefSeq (protein)	NP_000930 NP_001030333 NP_001306133 NP_001306134	NP_001265510 NP_001265511 NP_001265512 NP_001265513 NP_032921
Location (UCSC)	Chr 2: 25.16 – 25.17 Mb	Chr 12: 3.95 – 3.96 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

Function[edit]

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

• 
  α-MSH produced by neurons in the ventromedial nucleus has important roles in the regulation of appetite (POMC neuron stimulation results in satiety.^[5]) and sexual behavior, while α-MSH secreted from the intermediate lobe of the pituitary regulates the production of melanin.


• 
  ACTH is a peptide hormone that regulates the secretion of glucocorticoids from the adrenal cortex.


• 
  β-Endorphin and [Met]enkephalin are endogenous opioid peptides with widespread actions in the brain.

Synthesis[edit]

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 subtilisin-like enzymes known as prohormone convertases. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary, where four cleavage sites are used; adrenocorticotrophin (ACTH), essential for normal 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 prohormone convertase 1 (PC1), prohormone convertase 2 (PC2), 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 hypothalamus, placenta, and epithelium, all cleavage sites may be used, giving rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation. These include several distinct melanotropins, lipotropins, and endorphins that are contained within the adrenocorticotrophin and β-lipotropin peptides.

It is synthesized by:

• 
  Corticotrope cells of the anterior pituitary gland


• 
  Melanotrope cells of the intermediate lobe of the pituitary gland


• Neurons in the arcuate nucleus of the hypothalamus^[6]


• Smaller populations of neurons in the dorsomedial hypothalamus and brainstem
  


• 
  Melanocytes in the skin

Derivatives[edit]

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

• 
  N-Terminal Peptide of Proopiomelanocortin (NPP, or pro-γ-MSH)


• 
  α-Melanotropin (α-Melanocyte-Stimulating Hormone, or α-MSH)


• 
  β-Melanotropin (β-MSH)


• 
  γ-Melanotropin (γ-MSH)


• 
  𝛿-Melanocyte-Stimulating Hormone (𝛿-MSH, present in sharks [1])


• ε-Melanocyte-Stimulating Hormone (ε-MSH, present in some teleosts ^[7])


• 
  Corticotropin (Adrenocorticotropic Hormone, or ACTH)


• 
  Corticotropin-like Intermediate Peptide (CLIP)


• 
  β-Lipotropin (β-LPH)


• 
  Gamma Lipotropin (γ-LPH)


• β-Endorphin


• [Met]Enkephalin

Although the N-terminal 5 amino acids of β-endorphin are identical to the sequence of [Met]enkephalin, it is not generally thought that β-endorphin is converted into [Met]enkephalin.^{[citation needed]} Instead, [Met]enkephalin is produced from its own precursor, 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[edit]

Mutations in this gene have been associated with early onset obesity,^[8]adrenal insufficiency, and red hair pigmentation.^[9]

A study concluded that a polymorphism was associated with higher fasting insulin levels in the obese patients only. These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects indicating a possible gene-environment interaction. POMC variant may be involved in the natural history of polygenic obesity, contributing to the link between type 2 diabetes and obesity.^[10]

Dogs[edit]

A deletion mutation common in Labrador Retriever and Flat-Coated Retriever dogs is associated with increased interest in food and subsequent obesity.^[11]

Drug target[edit]

POMC is used as a target for a medication used to treat obesity in humans. The combination of bupropion and naltrexone acts via hypothalamic POMC neurons to decrease appetite.^[12]

Two humans with POMC deficiency have been treated with setmelanotide, a melanocortin-4 receptor agonist.^[13]

Interactions[edit]

Proopiomelanocortin has been shown to interact with melanocortin 4 receptor.^[14][15] The endogenous agonists of melanocortin 4 receptor include α-MSH, β-MSH, γ-MSH, and ACTH. The fact that these are all cleavage products of POMC should suggest likely mechanisms of this interaction.

See also[edit]

• Afamelanotide


• Agouti-related peptide


• Melanocortin


• Melanotan II

References[edit]

Further reading[edit]

External links[edit]

• 
  Pro-Opiomelanocortin at the US National Library of Medicine Medical Subject Headings (MeSH)

 This article incorporates public domain material from the National Center for Biotechnology Information website https://www.ncbi.nlm.nih.gov/RefSeq/ (Reference Sequence collection).