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0  structures 81  species 0  interactions 113  sequences 7  architectures

Family: Op_neuropeptide (PF08035)

Summary: Opioids neuropeptide

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Proopiomelanocortin". More...

Proopiomelanocortin Edit Wikipedia article

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)
Chromosome 2 (human)
Chr. Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for POMC
Genomic location for POMC
Band 2p23.3 Start 25,160,853 bp[1]
End 25,168,903 bp[1]
RNA expression pattern
PBB GE POMC 205720 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
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 Mb Chr 12: 3.95 – 3.96 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Opioids neuropeptide
Identifiers
Symbol Op_neuropeptide
Pfam PF08035
InterPro IPR013532
PROSITE PDOC00964

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

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:

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 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:

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 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

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

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

Two humans with POMC deficiency have been treated with setmelanotide, a melanocortin-4 receptor agonist.[12]

Interactions

Proopiomelanocortin has been shown to interact with melanocortin 4 receptor.[13][14]

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:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Varela L, Horvath TL (2012). "Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis". EMBO Reports. 13 (12): 1079–1086. doi:10.1038/embor.2012.174. PMC 3512417Freely accessible. PMID 23146889.  More than one of |pmc= and |PMC= specified (help)
  6. ^ Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (May 2001). "Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus". Nature. 411 (6836): 480–4. doi:10.1038/35078085. PMID 11373681. 
  7. ^ Harris RM, Dijkstra PD, Hofmann HA (January 2014). "Complex structural and regulatory evolution of the pro-opiomelanocortin gene family". General and Comparative Endocrinology. 195: 107–15. doi:10.1016/j.ygcen.2013.10.007. PMID 24188887. 
  8. ^ Kuehnen P, Mischke M, Wiegand S, Sers C, Horsthemke B, Lau S, Keil T, Lee YA, Grueters A, Krude H (2012). "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. PMC 3305357Freely accessible. PMID 22438814. 
  9. ^ "Entrez Gene: POMC proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)". 
  10. ^ Mohamed, F. E. B., Hamza, R. T., Amr, N. H., Youssef, A. M., Kamal, T. M., & Mahmoud, R. A. (2016). Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and adolescents. Egyptian Journal of Medical Human Genetics.
  11. ^ Raffan E, Dennis RJ, O'Donovan CJ, Becker JM, Scott RA, Smith SP, Withers DJ, Wood CJ, Conci E, Clements DN, Summers KM, German AJ, Mellersh CS, Arendt ML, Iyemere VP, Withers E, Söder J, Wernersson S, Andersson G, Lindblad-Toh K, Yeo GS, O'Rahilly S (May 2016). "A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs". Cell Metabolism. 23 (5): 893–900. doi:10.1016/j.cmet.2016.04.012. PMC 4873617Freely accessible. PMID 27157046. 
  12. ^ Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H (July 2016). "Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist". The New England Journal of Medicine. 375 (3): 240–6. doi:10.1056/NEJMoa1512693. PMID 27468060. 
  13. ^ Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR, Mosley R, Van Der Ploeg LH, Gantz I (December 2000). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry. 39 (48): 14900–11. doi:10.1021/bi001684q. PMID 11101306. 
  14. ^ Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I (March 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Molecular Endocrinology. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374. 

Further reading

External links

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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.

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

Domain organisation

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(11)
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(38)
RP55
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(12)
Full
(113)
Representative proteomes UniProt
(1466)
NCBI
(1608)
Meta
(0)
RP15
(11)
RP35
(38)
RP55
(84)
RP75
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  Seed
(12)
Full
(113)
Representative proteomes UniProt
(1466)
NCBI
(1608)
Meta
(0)
RP15
(11)
RP35
(38)
RP55
(84)
RP75
(104)
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Seed source: Prosite
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Lee SC
Number in seed: 12
Number in full: 113
Average length of the domain: 28.30 aa
Average identity of full alignment: 72 %
Average coverage of the sequence by the domain: 11.93 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.4 20.4
Trusted cut-off 20.7 24.8
Noise cut-off 20.0 19.9
Model length: 30
Family (HMM) version: 11
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