Proopiomelanocortin

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Proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)
Identifiers
Symbols	POMC; LPH; MSH; ACTH; CLIP; NPP; POC
External IDs	OMIM: 176830 MGI: 97742 HomoloGene: 723 GeneCards: POMC Gene
Gene Ontology Molecular function • hormone activity Cellular component • extracellular region • soluble fraction Biological process • generation of precursor metabolites and energy • signal transduction • neuropeptide signaling pathway • cell-cell signaling • blood pressure regulation Sources: Amigo / EGO
RNA expression pattern
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5443	18976
Ensembl	ENSG00000115138	ENSMUSG00000020660
UniProt	P01189	P01193
RefSeq (mRNA)	NM_000939	NM_008895
RefSeq (protein)	NP_000930	NP_032921
Location (UCSC)	Chr 2: 25.24 - 25.25 Mb	Chr 12: 3.95 - 3.96 Mb
PubMed search	[1]	[2]

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues.

This gene encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. There are 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. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary where four cleavage sites are used; adrenocorticotrophin, essential for normal steroidogenesis and the maintenance of normal adrenal weight, and lipotropin beta are the major end products.

In other 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 beta-lipotropin peptides.

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

Production

It is synthesized by:

• Corticotrope cells of the anterior pituitary gland
• Melanotrope cells of the intermediate lobe of the pituitary gland
• About 3000 neurons in the arcuate nucleus of the hypothalamus
• Smaller populations of neurons in the dorsomedial hypothalamus and brainstem
• Melanocytes in the skin

Derivatives

proopiomelanocortin derivatives
POMC
γ-MSH	ACTH		β-lipotropin
	α-MSH	CLIP	γ-lipotropin		β-endorphin
				β-MSH

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

• Adrenocorticotropic hormone (ACTH) and β-LPH in the anterior pituitary gland
• CLIP, γ-LPH, α-MSH and β-endorphin in the intermediate lobe
  • γ-MSH
  • β-MSH

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

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.

Function

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 arcuate nucleus has important roles in the regulation of appetite 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.

Interactions

Proopiomelanocortin has been shown to interact with Melanocortin 4 receptor.

See also

• Melanocortin
• Afamelanotide
• Melanotan II

Further reading

• Millington GW (2007). "The role of proopiomelanocortin (POMC) neurones in feeding behaviour". Nutr Metab (Lond). 4: 18. doi:10.1186/1743-7075-4-18. PMC 2018708 Freely accessible. PMID 17764572. 
• Bhardwaj RS, Luger TA (1995). "Proopiomelanocortin production by epidermal cells: evidence for an immune neuroendocrine network in the epidermis". Arch. Dermatol. Res. 287 (1): 85–90. doi:10.1007/BF00370724. PMID 7726641. 
• Raffin-Sanson ML, de Keyzer Y, Bertagna X (2003). "Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions". Eur. J. Endocrinol. 149 (2): 79–90. doi:10.1530/eje.0.1490079. PMID 12887283. CS1 maint: Multiple names: authors list (link)
• Dores RM, Lecaude S (2005). "Trends in the evolution of the proopiomelanocortin gene". Gen. Comp. Endocrinol. 142 (1-2): 81–93. doi:10.1016/j.ygcen.2005.02.003. PMID 15862552. 
• König S, Luger TA, Scholzen TE (2006). "Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and alpha-melanocyte-stimulating hormone in the skin". Exp. Dermatol. 15 (10): 751–61. doi:10.1111/j.1600-0625.2006.00472.x. PMID 16984256. CS1 maint: Multiple names: authors list (link)
• Farooqi S, O'Rahilly S (2007). "Genetics of obesity in humans". Endocr. Rev. 27 (7): 710–18. doi:10.1210/er.2006-0040. PMID 17122358. 

External links

• MeSH Pro-Opiomelanocortin

 This article incorporates public domain material from websites or documents of the National Center for Biotechnology Information (Reference Sequence collection).

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