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0  structures 291  species 0  interactions 584  sequences 5  architectures

Family: Op_neuropeptide (PF08035)

Summary: Opioids neuropeptide

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

Proopiomelanocortin Edit Wikipedia article

Proopiomelanocortin
Identifiers
Symbols POMC; ACTH; CLIP; LPH; MSH; NPP; POC
External IDs OMIM176830 MGI97742 HomoloGene723 GeneCards: POMC Gene
RNA expression pattern
PBB GE POMC 205720 at tn.png
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:
25.38 – 25.39 Mb
Chr 12:
3.95 – 3.96 Mb
PubMed search [1] [2]
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 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[edit]

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[edit]

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[edit]

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[edit]

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.[2][3]

Interactions[edit]

Proopiomelanocortin has been shown to interact with melanocortin 4 receptor.[4][5]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ "Entrez Gene: POMC proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)". 
  3. ^ 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". In Yeo, Giles S. H. PLoS Genet. 8 (3): e1002543. doi:10.1371/journal.pgen.1002543. PMC 3305357. PMID 22438814. 
  4. ^ 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. 
  5. ^ 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". Mol. Endocrinol. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374. 

Further reading[edit]

External links[edit]

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

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

Domain organisation

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Alignments

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(14)
Full
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RP35
(4)
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  Seed
(14)
Full
(584)
Representative proteomes NCBI
(585)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(9)
RP75
(25)
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  Seed
(14)
Full
(584)
Representative proteomes NCBI
(585)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(9)
RP75
(25)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.4 20.4
Trusted cut-off 20.4 22.5
Noise cut-off 20.3 19.6
Model length: 31
Family (HMM) version: 6
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Species distribution

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