Summary: Opioids neuropeptide
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Proopiomelanocortin Edit Wikipedia article
|RNA expression pattern|
Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 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 signal peptide sequence during translation.
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.
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.
It is synthesized by:
- Corticotrope cells of the anterior pituitary gland
- Melanotrope cells of the intermediate lobe of the pituitary gland
- 3,148±62 neurons in the arcuate nucleus of the hypothalamus
- Smaller populations of neurons in the dorsomedial hypothalamus and brainstem
- Melanocytes in the skin
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)
- γ-Melanotropin (γ-MSH)
- 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)
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. 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.
- 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.
 See also
- "Entrez Gene: POMC proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)".
- Kuehnen, Peter; Mischke, Mona, Wiegand, Susanna, Sers, Christine, Horsthemke, Bernhard, Lau, Susanne, Keil, Thomas, Lee, Young-Ae, Grueters, Annette, Krude, Heiko, Yeo, Giles S. H. (NaN undefined NaN). "An Alu Element–Associated Hypermethylation Variant of the POMC Gene Is Associated with Childhood Obesity". PLoS Genetics 8 (3): e1002543. doi:10.1371/journal.pgen.1002543.
- Cowley et al, Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus, Nature. 2001 May 24;411(6836):480-4.
- Yang, Y K; Fong T M, Dickinson C J, Mao C, Li J Y, Tota M R, Mosley R, Van Der Ploeg L H, Gantz I (December 2000). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry (UNITED STATES) 39 (48): 14900–11. doi:10.1021/bi001684q. ISSN 0006-2960. PMID 11101306.
- Yang, Y K; Ollmann M M, Wilson B D, Dickinson C, Yamada T, Barsh G S, Gantz I (March 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Mol. Endocrinol. (UNITED STATES) 11 (3): 274–80. doi:10.1210/me.11.3.274. ISSN 0888-8809. PMID 9058374.
 Further reading
- Millington GW (May 2006). "Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors". Clin. Exp. Dermatol. 31 (3): 407–12. doi:10.1111/j.1365-2230.2006.02128.x. PMID 16681590.
- 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. 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.
- 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.
- 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.
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Opioids neuropeptide Provide feedback
This family corresponds to the conserved YGG motif that is found in a wide variety of opioid neuropeptides such as enkephalin.
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR013532
Pro-opiomelanocortin is present in high levels in the pituitary and is processed into 3 major peptide families: adrenocorticotrophin (ACTH); alpha-, beta- and gamma-melanocyte- stimulating hormones (MSH); and beta-endorphin [PUBMED:2266117]. ACTH regulates the synthesis and release of glucocorticoids and, to some extent, aldosterone in the adrenal cortex. It is synthesised and released in response to corticotrophin-releasing factor at times of stress (i.e. heat, cold, infection, etc.), its release leading to increased metabolism. The action of MSH in man is poorly understood, but it may be involved in temperature regulation [PUBMED:2266117]. Full activity of ACTH resides in the first 20 N-terminal amino acids, the first 13 of which are identical to alpha-MSH [PUBMED:2266117, PUBMED:2839146].
This region corresponds to the conserved YGG motif that is found in a wide variety of opioid neuropeptides such as enkephalin
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Author:||Bateman A, Lee SC|
|Number in seed:||14|
|Number in full:||584|
|Average length of the domain:||23.60 aa|
|Average identity of full alignment:||87 %|
|Average coverage of the sequence by the domain:||11.63 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||6|
|Download:||download the raw HMM for this family|
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