Proopiomelanocortin

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Pro-opiomelanocortin
)
POMC
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
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 MbChr 12: 4 – 4.01 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Opioids neuropeptide
Identifiers
SymbolOp_neuropeptide
PfamPF08035
InterProIPR013532
PROSITEPDOC00964
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Pro-opiomelanocortin (POMC) is a precursor

polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation.[5] POMC is part of the central melanocortin system
.

Function

POMC is cut (cleaved) to give rise to multiple

vesicles that are released from the cells by exocytosis in response to appropriate stimulation:[citation needed
]

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

endorphins that are contained within the adrenocorticotrophin and β-lipotropin peptides.[citation needed
]

It is synthesized by:

Regulation by the photoperiod

The levels of proopiomelanocortin (pomc) are regulated indirectly in some animals by the

photoperiod. It is referred to[clarification needed] the hours of light during a day and it changes across the seasons. Its regulation depends on the pathway of thyroid hormones that is regulated directly by the photoperiod. An example are the siberian hamsters who experience physiological seasonal changes dependent on the photoperiod. During spring in this species, when there is more than 13 hours of light per day, iodothyronine deiodinase 2 (DIO2) promotes the conversion of the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3) through the removal of an iodine atom on the outer ring. It allows T3 to bind to the thyroid hormone receptor (TR), which then binds to thyroid hormone response elements (TREs) in the DNA sequence. The pomc proximal promoter sequence contains two thyroid-receptor 1b (Thrb) half-sites: TCC-TGG-TGA and TCA-CCT-GGA indicating that T3 may be capable of directly regulating pomc transcription. For this reason during spring and early summer, the level of pomc increases due to the increased level of T3.[8]

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]

Regulation of proopiomelanocortin by the photoperiod and thyroid hormones

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

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
:

Although the N-terminal 5 amino acids of

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

pigmentation.[14]

A study concluded that a

polygenic obesity, contributing to the link between type 2 diabetes and obesity.[15]

ACTH, an endproduct of POMC, but not in a suppression of POMC.[17]

Dogs

A deletion mutation common in

Flat-Coated Retriever dogs is associated with increased interest in food and subsequent obesity.[18]

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

γ-MSH, and ACTH. The fact that these are all cleavage products of POMC should suggest likely mechanisms of this interaction.[citation needed
]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115138 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020660 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "pro-opiomelanocortin preproprotein [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 30 December 2020.
  6. PMID 23146889
    .
  7. .
  8. .
  9. .
  10. .
  11. .
  12. , retrieved 2022-01-12
  13. .
  14. ^ "POMC proopiomelanocortin". Entrez Gene.
  15. .
  16. .
  17. .
  18. .
  19. .
  20. .
  21. .
  22. .

Further reading

External links

Public Domain This article incorporates public domain material from Reference Sequence collection. National Center for Biotechnology Information.