Proopiomelanocortin
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 2: 25.16 – 25.17 Mb | Chr 12: 4 – 4.01 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Opioids neuropeptide | |||||||||
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Identifiers | |||||||||
Symbol | Op_neuropeptide | ||||||||
Pfam | PF08035 | ||||||||
InterPro | IPR013532 | ||||||||
PROSITE | PDOC00964 | ||||||||
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Pro-opiomelanocortin (POMC) is a precursor
Function
POMC is cut (cleaved) to give rise to multiple
- pituitary regulates the movement of melaninproduced from melanocytes in skin.
- ACTH can also regulate secretion of gonadocorticoids from the cells of the zona reticularissince they also express ACTH receptors.
- opioid peptideswith 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
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
It is synthesized by:
- Corticotrope cells of the anterior pituitarygland
- pituitarygland
- Neurons in the arcuate nucleus of the hypothalamus[7]
- Smaller populations of neurons in the dorsomedial hypothalamus and brainstem
- Melanocytes in the skin[citation needed]
Regulation by the photoperiod
The levels of proopiomelanocortin (pomc) are regulated indirectly in some animals by the
However, during autumn and winter, when there is less than 13 hours of light per day, iodothyronine desiodinase 3 removes an iodine atom which converts thyroxine to the inactive reverse triiodothyronine (rT3), or which converts the active triiodothyronine to diiodothyronine (T2). Consequently, there is less T3 and it blocks the transcription of pomc, which reduces its levels during these seasons.[9]
Influences of photoperiods on relevant similar biological endocrine changes that demonstrate modifications of thyroid hormone regulation in humans have yet to be adequately documented.
Derivatives
POMC | |||||||||
γ-MSH | ACTH | β-lipotropin | |||||||
α-MSH | CLIP | γ-lipotropin | β-endorphin |
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β-MSH |
The large molecule of POMC is the source of several important biologically active substances . POMC can be cleaved enzymatically into the following
- 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[10])
- ε-Melanocyte-Stimulating Hormone (ε-MSH, present in some teleosts [11])
- 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
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
A study concluded that a
Dogs
A deletion mutation common in
Drug target
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.[19]
Two humans with POMC deficiency have been treated with setmelanotide, a melanocortin-4 receptor agonist.[20]
Interactions
Proopiomelanocortin has been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000115138 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020660 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "pro-opiomelanocortin preproprotein [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 30 December 2020.
- PMID 23146889.
- S2CID 4342893.
- S2CID 28088190.
- PMID 31189592.
- PMID 12899848.
- PMID 24188887.
- PMID 32491696, retrieved 2022-01-12
- PMID 22438814.
- ^ "POMC proopiomelanocortin". Entrez Gene.
- .
- PMID 33593393.
- PMID 34698826.
- PMID 27157046.
- PMID 24754973.
- PMID 27468060.
- PMID 11101306.
- PMID 9058374.
Further reading
- Millington GW (May 2006). "Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors". Clinical and Experimental Dermatology. 31 (3): 407–12. S2CID 25213876.
- Millington GW (September 2007). "The role of proopiomelanocortin (POMC) neurones in feeding behaviour". Nutrition & Metabolism. 4: 18. PMID 17764572.
- Bhardwaj RS, Luger TA (1994). "Proopiomelanocortin production by epidermal cells: evidence for an immune neuroendocrine network in the epidermis". Archives of Dermatological Research. 287 (1): 85–90. S2CID 33604397.
- Raffin-Sanson ML, de Keyzer Y, Bertagna X (August 2003). "Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions". European Journal of Endocrinology. 149 (2): 79–90. PMID 12887283.
- Dores RM, Lecaude S (May 2005). "Trends in the evolution of the proopiomelanocortin gene". General and Comparative Endocrinology. 142 (1–2): 81–93. PMID 15862552.
- König S, Luger TA, Scholzen TE (October 2006). "Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and alpha-melanocyte-stimulating hormone in the skin". Experimental Dermatology. 15 (10): 751–61. S2CID 32034934.
- Farooqi S, O'Rahilly S (December 2006). "Genetics of obesity in humans". Endocrine Reviews. 27 (7): 710–18. PMID 17122358.
External links
- Pro-Opiomelanocortin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P01189 (Pro-opiomelanocortin) at the PDBe-KB.
This article incorporates public domain material from Reference Sequence collection. National Center for Biotechnology Information.